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    Medical management of hiv infection Medical management of hiv infection Document Transcript

    • Go to a Chapter Table of Contents Natural Historyand Classification Laboratory Tests Disease Prevention Antiretroviral TherapyManagement of Opportunistic Infections Drugs: Guide to Information SystemsReview HIV in Corrections Medical Management of HIV Infection by John G. Bartlett, M.D. and Joel E. Gallant, M.D., M.P.H. The 2001-2002 edition of Medical Management of HIV Infection serves as the standard of care Hopkins AIDS Service and has been accepted as the standard of care for quality assurance by Medicaid. The full text of the book is included here. Throughout the chapter, red text indicates changes and updates made to the book for the 2001 Changes will stay highlighted in red for 3 months. Chapter I: Natural History and Classification To order a copy of the 2001-2002 Medical Chapter II: Laboratory Tests Management of HIV Infection: Call 1-800-787-1254 or order online. Chapter III: Disease Prevention: Prophylactic Antimicrobial Agents and V Each book costs $8.00, which includes the charge for shipping and handling. An invoice will be sent Chapter IV: Antiretroviral Therapy with the book(s). Credit card payments not accepted. Chapter V: Management of Opportunistic Infections and Miscellaneous C Production of the 2001-2002 edition of Medical Chapter VI: Drugs: Guide to Information Management of HIV Infection has been underwritten by an unrestricted educational grant from GlaxoSmithKline, Inc. Chapter VII: Systems Review HIV in Corrections from the 2000-2001 editionCopyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rights reserved.* Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained in this site because noor service can take the place of medical training, education, and experience. Consumers are cautioned that this site is not intended to provide medicalspecific medical condition they may have or treatment they may need and they are encouraged to call or see their physician or other health care providany health related questions they may have.
    • Go to a Chapter Table of Contents Natural History and Classification Tests Disease Prevention Antiretroviral Therapy Management of Opp Infections Drugs: Guide to Information Systems Review HIV in CorrecNote: Throughout the chapter, red text indicates changes and updates made to the book for the 20edition. Changes will stay highlighted in red for 3 months. Last updated 11/1/2001 I. Natural History and Classification Stages Table 1-1: Correlation of Complications with CD4 Cell Counts Table 1-2: HIV Infection - Signs and Symptoms Table 1-3: AIDS Surveillance Case Definition Table 1-4: Indicator Conditions in Case Definition of AIDS (Adults) 1997 To order a copy of the 2001-2002 Medical Management of HIV Infection : Call 1-800-787-1254 or order online. Each book costs $8.00, which includes the charge for shipping and handling. An invoice will be sent with the book(s). Credit card payments not accepted. Production of the 2001-2002 edition of Medical Management of HIV Infection has been underwritten by an unrestricted educational grant from GlaxoSmithKline, Inc. Copyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rights reserved. * Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained in this site because n reference or service can take the place of medical training, education, and experience. Consumers are cautioned that this site is not intended to provi advice about any specific medical condition they may have or treatment they may need and they are encouraged to call or see their physician or othe provider promptly with any health related questions they may have.
    • Go to a Chapter Table of Contents Natural History and Classification Tests Disease Prevention Antiretroviral Therapy Management of Opp Infections Drugs: Guide to Information Systems Review HIV in CorrecNote: Throughout the chapter, red text indicates changes and updates made to the book for the 20edition. Changes will stay highlighted in red for 3 months. Last updated 11/1/2001 II. Laboratory Tests HIV Types and Subtypes HIV Serology Alternative HIV Serologic Tests Quantitative Plasma HIV RNA CD4 Cell Count Resistance Testing Screening Battery Complete Blood Count Serum Chemistry Panel Syphilis Serology Chest X-Ray PPD Skin Testing PAP Smears Serology for Hepatitis B Virus (HBV) Testing for Hepatitis C Virus To order a copy of the 2001-2002 Medical Toxoplasmosis Serology Management of HIV Infection: Call 1-800-787-1254 Cytomegalovirus Serology or order online. Glucose-6-Phosphate Dehydrogenase Levels Adverse Drug Reaction Monitoring Each book costs $8.00, which includes the charge for shipping and handling. An invoice will be sent with the book(s). Credit card payments not accepted. Tables Table 2-1: Test for HIV-1 Table 2-2: Comparison Between Assay Methods for Viral Load Table 2-3: Comparison of Genotypic and Phenotypic Assays Production of the 2001-2002 edition of Medical Management of HIV Infection has been underwritten by Table 2-4: Letter Designations for Amino Acids an unrestricted educational grant from Table 2-5: Resistance Mutations GlaxoSmithKline, Inc. Table 2-6: Routine Laboratory Test in Asymptomatic Patients Table 2-7: Recommendations for Intervention Based on Results of PAP Smear Table 2-8: Tests for HCVCopyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rights reserved.* Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained in this site because noor service can take the place of medical training, education, and experience. Consumers are cautioned that this site is not intended to provide medicalspecific medical condition they may have or treatment they may need and they are encouraged to call or see their physician or other health care providany health related questions they may have.
    • Go to a Chapter Table of Contents Natural History and Classification Tests Disease Prevention Antiretroviral Therapy Management of Opp Infections Drugs: Guide to Information Systems Review HIV in CorrecNote: Throughout the chapter, red text indicates changes and updates made to the book for the 20edition. Changes will stay highlighted in red for 3 months. Last updated 11/1/2001 IV. Antiretroviral Therapy Recommendations for Antiretroviral Therapy Goals of Therapy Terms and Concepts Antiretroviral Therapy for HIV Infected Patients Recommendations for Antiretroviral Therapy in Pregnancy Postexposure Prophylaxis for Health Care Workers Postexposure Prophylaxis for Sexual Contact or Needle Sharing Antiretroviral Agents Nucleoside Analogs Non-nucleoside Reverse Transcriptase Inhibitors (NNRTI) Protease InhibitorsTo order a copy of the 2001-2002 Medical Class Adverse Reactions to Antiretroviral AgentsManagement of HIV Infection:Call 1-800-787-1254or order online. TablesEach book costs $8.00, which includes the charge forshipping and handling. An invoice will be sent with the Table 4-16: Antiretroviral Drugs Approved by FDA for HIVbook(s). Credit card payments not accepted. Table 4-20: Drugs That Should Not be Used with Protease Inhibitors or NNRTIs* Table 4-21: Drug Interactions Requiring Dose Modifications or Cautious Use Table 4-22: Drug Interactions: Protease Inhibitors and Non-Nucleoside Reverse Transcriptase Inhib Drug on Levels (AUCs)/Dose Table 4-27: HIV-Related Drugs with Overlapping ToxicitiesProduction of the 2001-2002 edition of MedicalManagement of HIV Infection has been underwritten by Table 4-28: Dosing of Antiretroviral Agents in Renal and Hepatic Failurean unrestricted educational grant from Table 4-29: Characteristics of Antiretrovirals During DialysisGlaxoSmithKline, Inc.Copyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rights reserved.* Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained in this site because noreference or service can take the place of medical training, education, and experience. Consumers are cautioned that this site is not intended to providadvice about any specific medical condition they may have or treatment they may need and they are encouraged to call or see their physician or otherprovider promptly with any health related questions they may have.
    • Go to a Chapter Table of Contents Natural History and Classification Tests Disease Prevention Antiretroviral Therapy Management of Opp Infections Drugs: Guide to Information Systems Review HIV in CorrecNote: Throughout the chapter, red text indicates changes and updates made to the book for the 20highlighted in red for 3 months. Last updated 11/1/2001 V. Management of Opportunistic Infections and Other Complica Opportunistic Infections Table 5-1: Fungal Pneumocystis carinii, Aspergillosis, Candidiasis, Cryptococcal meningitis, Cryptoc Coccidioidomycosis, Penicilliosis marneffei Table 5-2: Parasitic Infections Toxoplasma gondii, Cryptosporidiosis, Isosporidiosis, Microsporidiosis Table 5-3: Mycobacterial Infections M. tuberculosis, M. avium, M. kansasii, M. haemophilum, M.gor malonoense, M. chelonei Table 5-4: Viruses Herpes simplex, Herpes zoster, Cytomegalovirus retinitis, Progressive multifo Table 5-5: Bacteria Streptococcus pneumoniae, Bartonella henselea/ quintana, Haemophilus Pseudomonas aeruginosa, Rhodococcus equi, Salmonella, Staphylococcus aureus, Treponema pallid To order a copy of the 2001-2002 Medical Management of HIV Infection: Call 1-800-787-1254 or order online. Table 5-6: Treatment of Miscellaneous and Non-Infectious Disease Compli Each book costs $8.00, which includes the charge for Table 5-6A: Cardiac Table 5-6H: Gastrointes shipping and handling. An invoice will be sent with the Table 5-6B: Pulmonary book(s). Credit card payments not accepted. Table 5-6I: Hepatobiliary Table 5-6C: Renal Table 5-6J: Wasting Table 5-6D: Neurologic Table 5-6K: Pain Table 5-6E: Hematologic Table 5-6L: Psychiatric a Table 5-6F: Tumors Table 5-6M: Terminal Illn Production of the 2001-2002 edition of Medical Table 5-6G: Dermatologic Management of HIV Infection has been underwritten by an unrestricted educational grant from GlaxoSmithKline, Inc. Copyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rights reserved. * Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained in this site because n medical training, education, and experience. Consumers are cautioned that this site is not intended to provide medical advice about any specific medi need and they are encouraged to call or see their physician or other health care provider promptly with any health related questions they may have.
    • Go to a Chapter Table of Contents Natural Historyand Classification Laboratory Tests Disease Prevention Antiretroviral TherapyManagement of Opportunistic Infections Drugs: Guide to Information SystemsReview HIV in Corrections Note: Throughout the chapter, red text indicates changes and updates made to the book for the 20 edition. Changes will stay highlighted in red for 3 months. Last updated 11/1/2001 VI: Drugs: Guide to Information Understanding Drug Profiles Antiretroviral Therapy for HIV-infected Patients A B Abacavir Bactrim Acyclovir Benzodiazepines Agenerase Biaxin Albendazole Bupropion Alprazolam Buspar Amphotericin B Buspirone Amprenavir Ancobon AndroGel Ativan Atorvastatin Atovaquone To order a copy of the 2001-2002 Medical Aventyl Management of HIV Infection: Azithromycin Call 1-800-787-1254 AZT or order online. Each book costs $8.00, which includes the D E charge for shipping and handling. An invoice will be sent with the book(s). Credit card payments Dalmane Efavirenz not accepted. Dapsone Enoxacin Daraprim Epivir Daunorubicin Epogen ddC Erythropoietin Production of the 2001-2002 edition of Medical ddI Ethambutol Management of HIV Infection has been Delavirdine underwritten by an unrestricted educational grant from GlaxoSmithKline, Inc. d4T Desyrel Didanosine Diflucan Doxycycline Dronabinol G H Ganciclovir Halcion G-CSF Humatin Gemfibrozil Hydroxyurea Growth Hormone K L
    • Copyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rightsreserved.* Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained inthis site because no single reference or service can take the place of medical training, education, and experience. Consumers arecautioned that this site is not intended to provide medical advice about any specific medical condition they may have or treatmentthey may need and they are encouraged to call or see their physician or other health care provider promptly with any health related
    • Go to a Chapter Table of Contents Natural Historyand Classification Laboratory Tests Disease Prevention Antiretroviral TherapyManagement of Opportunistic Infections Drugs: Guide to Information SystemsReview HIV in CorrectionsNote: Throughout the chapter, red text indicates changes and updates made to the book for the 20edition. Changes will stay highlighted in red for 3 months. Last updated 11/1/2001 VII. Systems Review · Specific Psychiatric Problems · Pulmonary Complications · Nervous System Complications · GI Complications · Dermatologic Compilcations · Wasting · CMV Retinis · Fever To order a copy of the 2001-2002 Medical Management of HIV Infection: Call 1-800-787-1254 or order online. Each book costs $8.00, which includes the charge for shipping and handling. An invoice will be sent with the book(s). Credit card payments not accepted. Production of the 2001-2002 edition of Medical Management of HIV Infection has been underwritten by an unrestricted educational grant from GlaxoSmithKline, Inc.Copyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rightsreserved.* Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained inthis site because no single reference or service can take the place of medical training, education, and experience. Consumers arecautioned that this site is not intended to provide medical advice about any specific medical condition they may have or treatmentthey may need and they are encouraged to call or see their physician or other health care provider promptly with any health relatedquestions they may have.
    • Go to a Chapter Table of Contents Natural History and Classification Tests Disease Prevention Antiretroviral Therapy Management of Opp Infections Drugs: Guide to Information Systems Review HIV in CorrecNote: Throughout the chapter, red text indicates changes and updates made to the book for the 20Changes will stay highlighted in red for 3 months. Green text indicates material that no longer appeof the book. Last updated 6/1/2001 HIV in Corrections from the 2000-2001 Edition Testing Policies in Corrections Prevalence of HIV in Corrections Housing Issues for Inmates with HIV and AIDS Challenges and Opportunites with Treating HIV in Corrections Initial Medical Evaluation HIV Case Management within the Correctional Environment Medication Administration within the Prison System Telementoring & Telemedicine in Corrections To order a copy of the 2001-2002 Medical Management of HIV Infection : Call 1-800-787-1254 or order online. Each book costs $8.00, which includes the charge for shipping and handling. An invoice will be sent with the book(s). Credit card payments not accepted. Production of the 2001-2002 edition of Medical Management of HIV Infection has been underwritten by an unrestricted educational grant from GlaxoSmithKline, Inc. Copyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rights reserved. * Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained in this site because n take the place of medical training, education, and experience. Consumers are cautioned that this site is not intended to provide medical advice about may have or treatment they may need and they are encouraged to call or see their physician or other health care provider promptly with any health re
    • Copyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious DiseaseAIDS Service. All rights reserved. Permission NoticeRequests for permission to reprint, reproduce, and distribute documents and related graphics that athis website/are hosted on this server may be submitted by fax (410)-502-7915 or e-mail to MB HanThe names of the Johns Hopkins University, the Johns Hopkins University Infectious Diseases DivisJohns Hopkins AIDS Service web site or its faculty or staff may not be used in publicity or advertisinpermission. Exceptions to this include listings on web indexes, search engines, and related systemsThe Johns Hopkins University, The Johns Hopkins University School of Medicine and/or its DivisionInfectious Diseases and faculty and staff of the Johns Hopkins University cannot be held responsiblfor errors or inaccuracies in transcriptions, translations, or any other type of reproduction, alterationadulteration of material presented on any page of this web site (all pages filed under an internet addbeginning: http://hopkins-aids.edu, http://hopkins-aids.com, or http://hopkins-aids.org.) Editorial PolicyInformation contained on The Johns Hopkins AIDS Service web site is subjected to editorial reviewof the Johns Hopkins University, School of Medicine, Division of Infectious Diseases and AIDS Servfor accuracy, timeliness and relevance. Sponsors of this site are in no way involved with decisions rdesign, content, authorship, editorial policy, procedure, or practice. Commercial sponsorship noticessite and links to the web sites of commercial sponsors do not constitute endorsements of the compaand/or their products. Links are provided to other sites in order to provide ease of access to other inon the general subject matter. The editors make no representation as to the accuracy of the informathose sites. Editorial Board
    • John G. Bartlett, M.D.Joel E. Gallant, M.D., M.P.H.Richard E. Chaisson, M.D.Thomas C. Quinn, M.D.Richard D. Moore, M.D.Trish M. Perl, M.D., MS.c. StaffProject Development: Sharon McAvinueProject Management: Mary Beth Hansen, M.A.Design and Production: Lisa Darrah, Christine Stapf, Nicole Sokol, Laura Marcial DisclaimerThis web site is provided as a resource for physicians and other health care professionals in providiand treatment to patients with HIV/AIDS. Recommendations for care and treatment change rapidly aopinion can be controversial; therefore, physicians and other health care professionals are encouragconsult other sources and confirm the information contained within this site. Authors, editors, and prstaff will not be held liable for errors, omissions or inaccuracies in information or for any perceived husers of this site. It is up to the individual physician or other health care professional to use his/her bmedical judgment in determining appropriate patient care or treatment because no single referencecan take the place of medical training, education, and experience. Consumers are cautioned that thnot intended to provide medical advice about any specific medical condition they may have or treatmmay need, and they are encouraged to call or see their physician or other health care provider promany health related questions they may have. Consumers should never disregard medical advice or dseeking it because of something they have read on this web site.Information accessed through this online site is provided "AS IS" and without warranty, express or imimplied warranties of merchantability and fitness for a particular use or purpose are hereby excludedHopkins University School of Medicine, and the Johns Hopkins University Division of Infectious DiseAIDS Service make no warranty as to the reliability, accuracy, timeliness, usefulness or completeneinformation. Johns Hopkins University School of Medicine and the Johns Hopkins University DivisioInfectious Diseases and AIDS Service cannot and do not guarantee or warrant that files available fodownloading from this online site will be free of infection or viruses, worms, Trojan horses or other cmanifest contaminating or destructive properties.In addition, the content contained within any site linked to this web site is not the responsibility of ouand editors. Neither The Johns Hopkins University, The Johns Hopkins Health System Corporationindividual authors and editors are responsible for deletions or inaccuracies in information or for claimresulting from any such deletions or inaccuracies. Mention of specific drugs or products within this wdoes not constitute endorsement by editors, authors, The Johns Hopkins University Division of InfecDiseases or The Johns Hopkins University School of Medicine. With regard to specific drugs or prodphysicians are advised to consult their normal resources before prescribing to their patients.
    • and editors. Neither The Johns Hopkins University, The Johns Hopkins Health System Corporationindividual authors and editors are responsible for deletions or inaccuracies in information or for claimresulting from any such deletions or inaccuracies. Mention of specific drugs or products within this wdoes not constitute endorsement by editors, authors, The Johns Hopkins University Division of InfecDiseases or The Johns Hopkins University School of Medicine. With regard to specific drugs or prodphysicians are advised to consult their normal resources before prescribing to their patients. SponsorsThe Johns Hopkins University Division of Infectious Diseases and AIDS Service acknowledges andthe following sponsors for their support of this website. The following senior sponsors have providedgenerous, unrestricted educational grants:Bristol-Myers Squibb ImmunologyDuPont PharmaceuticalsRoche Virology Specialty Care Ortho BiotechMerck and GlaxoWellcome have also provided support for this website. Sponsors of this site are ininvolved with decisions regarding design, content, authorship, editorial policy, procedure, or practiceCommercial sponsorship notices on this site and links to the web sites of commercial sponsors do nconstitute endorsements of the companies and/or their products. Links are provided to other sites inprovide ease of access to other information on the general subject matter. The editors make norepresentation as to the accuracy of the information on those sites. Contact InformationQuestions about the site or feedback pertaining to its content, structure, navigation or overall functiomay be directed to the project manager, Mary Beth Hansen, M.A. Suggestions will be given appreciconsideration and all attempts will be made to reconcile errors or difficulties called to our attention; his not possible to answer all e-mail received through this site, so we extend our gratitude in advancethoughtful feedback.Those seeking answers to questions of a clinical nature are encouraged to refer to either the Patienthe Clinician Forum. Questions that cannot be addressed through either of those forums fall outsideparameters of this web site and will not be answered; readers are encouraged to seek their answerselsewhere.Note to Students: Please note that requests submitted by writers asking to be sent "all" informationspecific or general topic in order to complete a homework assignment, write a research paper, or prreport will not be answered. We are unable to send readers information; furthermore, students areencouraged to complete their own thorough searches for information and are reminded that the taskconducting research is the burden, responsibility and ultimate joy (or heartache) of the student, andno desire to diminish the richness of that experience.
    • Copyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rights reserved.* Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained in this site because no sor service can take the place of medical training, education, and experience. Consumers are cautioned that this site is not intended to provide medical aspecific medical condition they may have or treatment they may need and they are encouraged to call or see their physician or other health care provideany health related questions they may have.
    • Go to a Chapter Table of Contents Natural History and Classification Tests Disease Prevention Antiretroviral Therapy Management of Opp Infections Drugs: Guide to Information Systems Review HIV in Correc Chapter I: Natural History and Classification Stages Tables Table 1-1: Correlation of Complications with CD4 Cell Counts Table 1-2: HIV Infection - Signs and Symptoms Table 1-3: AIDS Surveillance Case Definition Table 1-4: Indicator Conditions in Case Definition of AIDS (Adults) 1997 StagesViral transmission Acute retroviral syndrome Recovery + serconversionAsymptomatic chronic HIV infection Symptomatic HIV infection/AIDS DeathFigure 1-1: Natural History of HIV Infection in an Average Patient WithoutAntiretroviral Therapy from the Time of HIV Transmission to Death at 10-11 YearsThe initial event is the acute retroviral syndrome, which is accompanied by a precipitous decline in CD4 cell counts (closed squares), high plasma viremcircles), and high concentrations of HIV RNA in plasma (closed triangles). Clinical recovery is accompanied by a reduction in plasma viremia, reflectingof cytotoxic T cell (CTL) response. The CD4 cell count gradually declines with a more accelerated decline 1.5 to 2 years before an AIDS-defining diagnconcentrations in plasma show an initial "burst" during acute infection and then decline to a "set point" as a result of seroconversion and development oresponse. With continued infeciton, HIV RNA levels then gradually increase (J Infect Dis 1999;180:1018). Late-stage disease is characterized by a CD<200/mm and the development of opportunistic infections, selected tumors, wasting, and neurologic complications. In an untreated patient, the median 3the CD4 cell count has fallen to <200/mm3 is 3.7 years; the median CD4 cell count at the time of the first AIDS-defining complication is 60-70/mm 3; thesurvival after an AIDS-defining complication is 1.3 years. (Figure reprinted with permission from Fauci AS, et al. Ann Intern Med, 1996;124:654).Return to top
    • Top of Page | Next page -- Table 1-1: Correlation of Complications with CD4 Cell CountsCopyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rights reserved.* Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained in this site because noreference or service can take the place of medical training, education, and experience. Consumers are cautioned that this site is not intended to providadvice about any specific medical condition they may have or treatment they may need and they are encouraged to call or see their physician or otherprovider promptly with any health related questions they may have.
    • Go to a Chapter Table of Contents Natural History and Classification Tests Disease Prevention Antiretroviral Therapy Management of Opp Infections Drugs: Guide to Information Systems Review HIV in Correc Chapter I: Natural History and Classification - Table 1-1 Stages Tables Table 1-1: Correlation of Complications with CD4 Cell Counts Table 1-2: HIV Infection - Signs and Symptoms Table 1-3: AIDS Surveillance Case Definition Table 1-4: Indicator Conditions in Case Definition of AIDS (Adults) 1997Table 1-1: Correlation of Complications With CD4 Cell Counts(see Arch Intern Med 1995;155:1537)CD4 Cell Count* Infectious Complications Noninfectious Complications>500/mm 3 Acute retroviral syndrome Persistent generalized lymphadenopathy (PGL) Candidal vaginitis Guillain-Barré syndrome Myopathy Aseptic meningitis200 - 500/mm 3 Pneumococcal and other Cervical intraepithelial neoplasia bacterial pneumonia Cervical cancer Pulmonary tuberculosis B-cell lymphoma Herpes zoster Anemia Oropharyngeal candidiasis (thrush) Mononeuronal multiplex Cryptosporidiosis, self-limited Idiopathic thrombocytopenic purpura Kaposis sarcoma Hodgkins lymphoma Oral hairy leukoplakia Lymphocytic interstitial pneumonitis<200/mm 3 Pneumocystis carinii pneumonia Wasting Disseminated histoplasmosis and Peripheral neuropathy coccidioidomycosis HIV-associated dementia Miliary/extrapulmonary TB Cardiomyopathy Progressive multifocal leukoencephalopathy (PML) Vacuolar myelopathy Progressive polyradiculopathy
    • HIV-associated dementia Miliary/extrapulmonary TB Cardiomyopathy Progressive multifocal leukoencephalopathy (PML) Vacuolar myelopathy Progressive polyradiculopathy<100/mm 3 Disseminated herpes simplex Toxoplasmosis Cryptococcosis Cryptococcosis, chronic Microsporidiosis Candida esophagitis<50/mm 3 Disseminated cytomegalorvirus (CMV) Central nervous system (CNS) lymphoma Disseminated Mycobacterium avium complex* Most complications occur with increasing frequency at lower CD4 cell counts. Some conditions listed as "Noninfectious" are probably associated with transmissible microbes: examples include lymphoma(Epstein-Barr virus [EBV]) and cervical canver (human papillomavirus [HPV]). Top of Page | Next page -- Table 1-2: Primary HIV Infection - Signs and SymptomsCopyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rights reserved.* Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained in this site because noreference or service can take the place of medical training, education, and experience. Consumers are cautioned that this site is not intended to providadvice about any specific medical condition they may have or treatment they may need and they are encouraged to call or see their physician or otherprovider promptly with any health related questions they may have.
    • Go to a Chapter Table of Contents Natural History and Classification Tests Disease Prevention Antiretroviral Therapy Management of Opp Infections Drugs: Guide to Information Systems Review HIV in Correc Chapter I: Natural History and Classification - Table 1-2 Stages Tables Table 1-1: Correlation of Complications with CD4 Cell Counts Table 1-2: HIV Infection - Signs and Symptoms Table 1-3: AIDS Surveillance Case Definition Table 1-4: Indicator Conditions in Case Definition of AIDS (Adults) 1997Table 1-2: Primary HIV Infection - Signs and Symptoms([Department of Health and Human ServicesGuidelines]http://www.hivatis.org, April 2001)Fever 96%Adenopathy 74%Pharyngitis 70%Rash* 70%Myalgias 54%Diarrhea 32%Headache 32%Nausea and vomiting 27%Hepatosplenomegaly 14%Weight loss 13%Thrush 12%Neurologic symptom 12%*Rash - Erythematous maculopapular rash on face and trunk, sometimesextremities, including palms and soles. Some have mucocutaneousulceration involving mouth, esophagus, or genitals. Aseptic meningitis, meningoencephalitis, peripheral neuropathy, facialpalsy, Guillain-Barré syndrome, brochial neuritis, cognitive impairment, orpsychosis.
    • Top of Page | Next page -- Table 1-3: AIDS Surveillance Case Definition for Adolescents and AduCopyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rights reserved.* Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained in this site because noreference or service can take the place of medical training, education, and experience. Consumers are cautioned that this site is not intended to providadvice about any specific medical condition they may have or treatment they may need and they are encouraged to call or see their physician or otherprovider promptly with any health related questions they may have.
    • Go to a Chapter Table of Contents Natural History and Classification Tests Disease Prevention Antiretroviral Therapy Management of Opp Infections Drugs: Guide to Information Systems Review HIV in Correc Chapter I: Natural History and Classification - Table 1-3 Stages Tables Table 1-1: Correlation of Complications with CD4 Cell Counts Table 1-2: HIV Infection - Signs and Symptoms Table 1-3: AIDS Surveillance Case Definition Table 1-4: Indicator Conditions in Case Definition of AIDS (Adults) 1997 Table 1-3: AIDS Surveillance Case Definition for Adolescents and Adults 1993 CD4 Cell Clinical Categories Categories A B C* Asymptomatic, Symptomatic AIDS Indicator or PGL or Acute Condition (not A or C) HIV Infection (1987) 1) >500/mm 3 A1 B1 C1 (>29%) 2) 200 to 499/mm 3 A2 B2 C2 (14% to 28%) 3) <200/mm 3 A3 B3 C3 (<14%)* All patients in categories A3, B3 and C1-3 defined as having AIDS, based on the presence of an AIDS-indicator condition (Table 1-4) and/or a CD4 ce<200/mm 3. Symptomatic conditions not included in Category C that are a) attributed to HIV infection or indicative of a defect in cell-mediated immunity, or b) consiclinical course or management that is complicated by HIV infection. Examples of B conditions include but are not limited to bacillary angiomatosis; thruscandidiasis which is persistent, frequent, or poorly responsive to therapy; cervical dysplasia (moderate or severe); cervical carcinoma in situ; constitutionsuch as fever (38.5º C) or diarrhea >1 month; oral hairy leukoplakia; herpes zoster involving two episodes or >1 dermatome; idiopathic thrombocytopen(ITP); listeriosis; pelvic inflammatory disease (PID) (especially if complicated by a tubo-ovarian abscess); and peripheral neuropathy.
    • Top of Page | Next page -- Table 1-4: Indicator Conditions in Case Definition of AIDS (Adults) -Copyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rights reserved.* Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained in this site because noor service can take the place of medical training, education, and experience. Consumers are cautioned that this site is not intended to provide medical aspecific medical condition they may have or treatment they may need and they are encouraged to call or see their physician or other health care provideany health related questions they may have.
    • Go to a Chapter Table of Contents Natural History and Classification Tests Disease Prevention Antiretroviral Therapy Management of Opp Infections Drugs: Guide to Information Systems Review HIV in Correc Chapter I: Natural History and Classification - Table 1-4 Stages Tables Table 1-1: Correlation of Complications with CD4 Cell Counts Table 1-2: HIV Infection - Signs and Symptoms Table 1-3: AIDS Surveillance Case Definition Table 1-4: Indicator Conditions in Case Definition of AIDS (Adults) 1997Table 1-4: Indicator Conditions in Case Definition of AIDS (Adults)-1997*Candidiasis of esophagus, trachea, bronchi, or lungs - 3846 (16%)Cervical cancer, invasive - 144 (0.6%)Coccidioidomycosis, extrapulmonary - 74 (0.3%)Cryptococcosis, extrapulmonary - 1168 (5%)Cryptosporidiosis with diarrhea >1 month - 314 (1.3%)CMV of any organ other than liver, spleen, or lymph nodes; eye - 1638 (7%)Herpes simplex with mucocutaneous ulcer >1 month or bronchitis, pneumonitis, esophagitis - 1250 (5%)Histoplasmosis, extrapulmonary - 208 (0.9%)HIV-associated dementia : Disabling cognitive and/or other dysfunction interfering with occupation or activities of daily living - 1196 (5%)HIV-associated wasting : Involuntary weight loss >10% of baseline plus chronic diarrhea (>2 loose stools/day >30 days) or chronic weakness and docenigmatic fever >30 days - 4212 (18%)Isoporosis with diarrhea >1 month - 22 (0.1%)Kaposis sarcoma in patient under 60 yrs (or over 60 yrs ) - 1500 (7%)Lymphoma, Burkitts - 162 (0.7%), immunoblastic - 518 (2.3%), primary CNS - 170 (0.7%)Mycobacterium avium, disseminated - 1124 (5%)Mycobacterium tuberculosis, pulmonary - 1621 (7%), extrapulmonary - 491 (2%)Nocardiosis - <1%Pneumocystis carinii pneumonia - 9145 (38%)Pneumonia, recurrent-bacterial (>2 episodes in 12 months) - 1347 (5%)Progressive multifocal leukoencephalopathy - 213 (1%)Salmonella septicemia (nontyphoid), recurrent - 68 (0.3%)
    • Pneumocystis carinii pneumonia - 9145 (38%)Pneumonia, recurrent-bacterial (>2 episodes in 12 months) - 1347 (5%)Progressive multifocal leukoencephalopathy - 213 (1%)Salmonella septicemia (nontyphoid), recurrent - 68 (0.3%)Strongyloidosis, extraintestinal - <1%Toxoplasmosis of internal organ - 1073 (4%)Wasting syndrome due to HIV (as defined above - HIV-associated wasting)* Indicates frequency as the AIDS-indicator condition among 42,350 reported cases in 1997. Numbers indicate sum of definitive and presumptive diagcondition. The number in parentheses is the percentage of all patients reported with an AIDS-defining diagnosis; these do not total 100%, since some hdiagnosis and many were reported based on the CD4 cell count criterion. See Viral Transmission. Requires positive HIV serology. Added in the revised case definition, 1993. Top of Page | Next page -- Chapter II: Laboratory TestsCopyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rights reserved.* Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained in this site because noor service can take the place of medical training, education, and experience. Consumers are cautioned that this site is not intended to provide medicalspecific medical condition they may have or treatment they may need and they are encouraged to call or see their physician or other health care providany health related questions they may have.
    • Go to a Chapter Table of Contents Natural History and Classification Tests Disease Prevention Antiretroviral Therapy Management of Opp Infections Drugs: Guide to Information Systems Review HIV in Correc Chapter II: Laboratory Tests Contents: HIV Types and Subtypes Chest X-Ray HIV Serology PPD Skin Testing Alternative HIV Serologic Tests PAP Smears Quantitative Plasma HIV RNA Serology for Hepatitis B Virus (HBV) CD4 Cell Count Testing for Hepatitis C Virus Resistance Testing Toxoplasmosis Serology Screening Battery Cytomegalovirus Serology Complete Blood Count Glucose-6-Phosphate Dehydrogenase Levels Serum Chemistry Panel Adverse Drug Reaction Monitoring Syphilis Serology Tables Table 2-1: Test for HIV-1 Table 2-2: Comparison Between Assay Methods for Viral Load Table 2-3: Comparison of Genotypic and Phenotypic Assays Table 2-4: Letter Designations for Amino Acids Table 2-5: Resistance Mutations Table 2-6: Routine Laboratory Test in Asymptomatic Patients Table 2-7: Recommendations for Intervention Based on Results of PAP Smear Table 2-8: Tests for HCVLaboratory tests recommended for initial evaluation and follow-up of all patients are summarized in and 2-6. HIV TYPES AND SUBTYPESHIV infection is established by detecting antibodies to the virus, viral antigens, viral RNA/DNA, or by(Lancet 1996;348:176). The standard test is for antibody detection. There are two types: HIV-1 andwhich show 40% to 60% amino acid homology. HIV-1 accounts for nearly all cases except a minoritstrains that originate in West Africa. HIV-1 is divided into subtypes or clades designated "A to K" (coreferred to as "M subtypes") and "O." Subtype O shows 55% to 70% homology with the M subtypesgroup of viruses labeled "N" for "new" have been reported (Nat Med 1998;4:1032; Science 2000;28Over 98% of HIV-1 infections in the United States are caused by clade B; most non-B subtypes in thStates were acquired in other countries (J Infect Dis 2000;181:470).Return to top HIV-2
    • HIV-2 is another human retrovirus that causes immune deficiency due to depletion of CD4 cells. It isfound in West Africa*. Compared to HIV-1, HIV-2 is less transmissible (5- to 8-fold less efficient thanearly-stage disease and rarely the cause of vertical transmission), is associated with a lower viral loassociated with a slower rate of both CD4 cell decline and clinical progression (Lancet 1994;344:131994;8[suppl 1]:585; J Infect Dis 1999;180:1116; J AIDS 2000;24:257; Arch Intern Med 2000;160:3patients with HIV-2 infections with CD4 cell counts have no detectable virus with viral load testing arelatively low viral loads with CD4 cell counts <500/mm3; some feel low viral replication may accounlower rate of transmission and longer period of clinical latency with HIV-2 infections (J AIDS 2000;2HIV-2 shows reduced homology with HIV-1 compared to HIV-1 subtypes (Nat Med 1987;328:543). Ato 30% of patients with HIV-2 infection have negative antibody tests depending on the enzymeimmunosorbent assay (EIA) tests used; Western blots (WBs) are weakly cross-reactive. WB for HIVneither well standardized nor FDA approved (Ann Intern Med 1993;118:211; JAMA 1992;267:2775)EIA was licensed by the FDA in 1990 and became mandatory for screening blood donors in 1992. Scommercial labs now use combination EIA screening assays to detect HIV-1 and HIV-2 simultaneoualthough this is not recommended for routine testing by the Centers for Disease Control and Preven(CDC) (MMWR 1992;41[RR-12]:1). Viral load tests are not generally available for HIV-2 (Arch Intern2000;160:3286). There were 78 persons diagnosed with HIV-2 infection in the United States betweeand January 1998: 52 were born in West Africa, and most of the rest had traveled there, had a sexufrom that region, or had incomplete data (MMWR 1995;44:603; JAMA 1992;267:2775). The CDCrecommends that HIV-2 serology be included in serologic testing of: 1) natives of endemic areas,* 2needle-sharing and sex partners of persons from an endemic area,* 3) sex partners or needle-sharipartners of persons with HIV-2 infection, 4) persons who received transfusions or nonsterile injectioendemic areas,* and 5) children of women with HIV-2 infection. Contact CDC for HIV-2 serologic tes*Endemic areas in West Africa - Benin, Burkina Faso, Cape Verde, Cote dIvoire, Gambia, Ghana, Guinea Guinea-BisMali, Mauritania, Niger, Nigeria, São Tome, Senegal, Sierra Leone, and Togo; other African countries - Angola and Mo(MMWR 1992;4[RR-12]:1).Return to top HIV SEROLOGY
    • Standard Test: The standard serologic test consists of a screening EIA followed by a confirmatoryEIA uses antigens prepared by lysis of whole virus, recombinant and/or synthetic peptides. The senspecificity of the tests are dictated by these preparations. Currently used EIA reagents are generallyrecombinant antigens that improve specificity and reduce the window period compared with earlierpreparations, but about 30% of infections with HIV-2 are falsely negative. The EIA screening test re"repeatedly reactive" test, which is the criterion for WB testing. WB detects antibodies to HIV-1 protincluding core (p17, p24, p55), polymerase (p31, p51, p66), and envelope (gp41, gp120, gp160). Wshould always be coupled with EIA screening; WB alone has a 2% rate of false positives. Results (2000;109:568) of WB are interpreted as: Negative: No bands Positive: Reactivity to gp41 + gp120/160 or p24 + gp120/160 Indeterminate: Prescence of any band pattern that does not meet criteria for positive resultsAccuracy: Standard serologic assays (EIA and WB or immunofluorescent assay [IFA]) show sensitspecificity rates of >98% (JAMA 1991;266:2861; Am J Med 2000;109:568). Positive tests should beconfirmed with repeat tests or with corroborating clinical or laboratory data.False-negative results: False-negative results are usually due to testing in the "window period." Fopopulation with high rates of seroconversion, such as injection drug users in Baltimore, who haveseroconversion rates of 3% to 4%/year, false-negative serology results occur in 0.3% (J Infect Dis1993;168:327). For a low seroprevalence group such as blood donors, false-negative results are mucommon (0.001%) (N Engl J Med 1991;325:1; N Engl J Med 1991;325:593). Causes of false-negatiinclude: The window period: The time delay from infection to positive EIA averages 10 to 14 days with test reagents (Clin Infect Dis 1997;25:101; Am J Med 2000;109:568). Some do not seroconve 4 weeks, but virtually all patients seroconvert within 6 months (Am J Med 2000;109:568). Prop with antiretroviral agents and acute hepatitis C infection may prolong the time from transmissio seroconversion. Seroreversion: Some patients serorevert in late-stage disease (JAMA 1993;269:2786; Ann Int 1988;108:785). Seroreversion may also occur in patients who achieve prolonged immune reco due to highly active antiretroviral therapy (HAART) (N Engl J Med 1999;340:1683). "Atypical host response" accounts for rare cases and is largely unexplained (AIDS 1995;9:95; 1996;45:181; Clin Infect Dis 1997;25:98). Agammaglobulinemia Type N or O strains or HIV-2: EIA screening tests may fail to detect the O subtype (Lancet 1994;343:1393; Lancet 1994;344:1333; MMWR 1996;45:561). This strain is rare; only one pa strain O HIV infection was detected in the United States through July 1996 (MMWR 1996;45:5 Emerg Infect Dis 1996;2:209). The N group is another variant that causes false-negative EIA s tests, but may be positive by WB (Nat Med 1998;4:1032). There have been no recognized infe with the N strain in the United States through March 2000 (J Infect Dis 2000;181:470). Standa screening tests are falsely negative in 20% to 30% of patients infected with HIV-2. Detection m require tests specifically for HIV-2. Risks for HIV-2 are summarized above. Technical or clerical errorFalse-positive results: The frequency of false-positive HIV serology in a low-prevalence populationmilitary recruits from rural United States) was 1/135,000 (0.0007%) (N Engl J Med 1988;319:961); fdonors in Minnesota it was 6/million (0.0006%) (Ann Intern Med 1989;110:617). A survey of 5 milliodonor samples obtained from 1991 to 1995 found that the prevalence of false positives was 0.0004%
    • Technical or clerical errorFalse-positive results: The frequency of false-positive HIV serology in a low-prevalence populationmilitary recruits from rural United States) was 1/135,000 (0.0007%) (N Engl J Med 1988;319:961); fdonors in Minnesota it was 6/million (0.0006%) (Ann Intern Med 1989;110:617). A survey of 5 milliodonor samples obtained from 1991 to 1995 found that the prevalence of false positives was 0.0004%251,000. The greatest source of error was a p31 band on WB, a band that has subsequently been dfrom the interpretive criteria (JAMA 1998;280:1080). Autoantibodies: A single case has been reported and was ascribed to autoantibodies in a patie lupus erythematosus and end-stage renal disease (N Engl J Med 1993;328:1281). A subsequ indicated that this patient did have HIV infection as verified by positive cultures (N Engl J Med 1994;331:881). Another patient with two positive tests and two indeterminate WB tests was fo uninfected with a negative HIV culture and PCR (Clin Infect Dis 1992;15:707). HIV vaccines: This is the most common cause of false-positive HIV serology. In an analysis of healthy volunteers in HIV vaccine studies, 68% had positive EIA tests and 0% to 44% had pos depending on the antigen in the vaccine (Ann Intern Med 1994;121:584). Factitious HIV infection: This refers to patients who report a history of a positive test that is err either due to misunderstanding or to intent to deceive (Ann Intern Med 1994;121:763). It is imp confirm anonymous tests and laboratory reports that cannot be obtained, using either repeat s viral load testing. [Note that 2% to 9% of viral load tests are falsely positive, usually with low v (Ann Intern Med 1999;130:37)]. Technical or Clerical ErrorIndeterminate results: Indeterminate test results account for 4% to 20% of WB assays with positivfor HIV-1 proteins. Causes of indeterminate results include: Serologic tests in the process of seroconversion; anti-p24 is usually the first antibody to appea Late-stage HIV infection, usually with loss of core antibody Cross-reacting nonspecific antibodies, as seen with collagen-vascular disease, autoimmune d lymphoma, liver disease, injection drug use, multiple sclerosis, parity, or recent immunization Infection with O strain or HIV-2 HIV vaccine recipients (see above) Technical or Clerical errorThe most important factor in evaluating indeterminate results is risk assessment. Patients in low-riskcategories with indeterminate tests are almost never infected with either HIV-1 or HIV-2; repeat testcontinues to show indeterminate results, and the cause of this pattern is infrequently established (NMed 1990;322:217). For this reason, such patients should be reassured that HIV infection is extremunlikely, although follow-up serology at 3 months is recommended to provide absolute assurance. Pwith indeterminate tests who are in the process of seroconversion usually have positive WBs withinrepeat tests at 1, 2, and 6 months are generally advocated with appropriate precautions to prevent vtransmission in the interim (J Gen Intern Med 1992;7:640; J Infect Dis 1991;164:656; Arch Intern M2000;160:2386; J AIDS 1998;17:376).Frequency of testing: Periodic tests are recommended for patients who practice high-risk behaviofrequency is arbitrary, but most suggest 6- to 12-month intervals. Annual seroconversion rates are eas follows: general population - 0.02%, military recruits - 0.04%, gay men - 0.5% to 2% (higher for ymen), and injection drug users in areas with high seroprevalence - 0.7% to 6% (Am J Epidemiol1991;134:1175; J AIDS 1993;6:1049; Arch Intern Med 1995;155:1305; Am J Public Health 1996;86Public Health 2000;90:352).
    • Top of Page | Next page -- Alternative HIV Serologic TestsCopyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rights reserved.* Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained in this site because no sor service can take the place of medical training, education, and experience. Consumers are cautioned that this site is not intended to provide medical aspecific medical condition they may have or treatment they may need and they are encouraged to call or see their physician or other health care provideany health related questions they may have.
    • Go to a Chapter Table of Contents Natural History and Classification Tests Disease Prevention Antiretroviral Therapy Management of Opp Infections Drugs: Guide to Information Systems Review HIV in Correc Chapter II: Laboratory Tests Contents: HIV Types and Subtypes Chest X-Ray HIV Serology PPD Skin Testing Alternative HIV Serologic Tests PAP Smears Quantitative Plasma HIV RNA Serology for Hepatitis B Virus (HBV) CD4 Cell Count Testing for Hepatitis C Virus Resistance Testing Toxoplasmosis Serology Screening Battery Cytomegalovirus Serology Complete Blood Count Glucose-6-Phosphate Dehydrogenase Levels Serum Chemistry Panel Adverse Drug Reaction Monitoring Syphilis Serology Tables Table 2-1: Test for HIV-1 Table 2-2: Comparison Between Assay Methods for Viral Load Table 2-3: Comparison of Genotypic and Phenotypic Assays Table 2-4: Letter Designations for Amino Acids Table 2-5: Resistance Mutations Table 2-6: Routine Laboratory Test in Asymptomatic Patients Table 2-7: Recommendations for Intervention Based on Results of PAP Smear Table 2-8: Tests for HCV Alternative HIV Serologic Tests (Table 2-1)IFA: This is another method to detect HIV antibodies using patient serum reacted with HIV-infectedusing a fluorochrome as the indicator method.Home Kits: Johnson & Johnson has withdrawn the Confide HIV Test, making Home Access Express(Home Access Health Corp., Hoffman Estates, III; 800-HIV-TEST) the only available home kit. Thissold in retail and on-line pharmacies at approximately $39.99 for routine mailing with results in 7 day$49.99 for Federal Express transport with results in 3 days. Blood is obtained by lancet, and a filterblotted blood is mailed in a protected envelope using an anonymous code. Home Access tests useEIA with a confirmatory IFA. Sensitivity and specificity approach 100%. Callers learn of a negative tethrough a prerecorded message, but the patient can access a representative to discuss results if deCallers with positive results receive counseling and health care referral from a counselor. In a study174,316 HIV home sample collection tests in 1996 to 1997, 0.9% were positive, and 97% of users ctheir results. Nearly 60% of all users and 49% of HIV-positive persons had never previously been te(JAMA 1998;280:1699). Merits of this type of home testing are debated (N Engl J Med 1995;332:12Rapid Tests: SUDS (Abbott Diagnostics) is the only FDA-approved rapid test for HIV (On October 17Abbott Diagnostics notified customers that the SUDS test was not available due to "manufacturing pand time of availability is not known). SUDS must be performed by a trained laboratory technician aare available in 10 to 15 minutes. Studies with 6200 specimens demonstrated that the sensitivity isthe specificity is 99.6% (J AIDS 1993;6:115; Am J Emerg Med 1991;9:416; Ann Intern Med 1996;12Based on these studies of sensitivity and specificity, it is recommended that negative results be repodefinitive, but that positive results be confirmed with standard serology. The cost is $9/test, but twomust be included, so the true cost is $27 for one test and $36 for two. This test is recommended fordetermining the serologic status of the source in healthcare worker exposures, for pregnant womenpresent in labor and have not been tested, and for patients who are unlikely to return for test resultspatients seen in sexually transmitted disease (STD) clinics, emergency rooms, etc. (MMWR 1998;4
    • Based on these studies of sensitivity and specificity, it is recommended that negative results be repodefinitive, but that positive results be confirmed with standard serology. The cost is $9/test, but twomust be included, so the true cost is $27 for one test and $36 for two. This test is recommended fordetermining the serologic status of the source in healthcare worker exposures, for pregnant womenpresent in labor and have not been tested, and for patients who are unlikely to return for test resultspatients seen in sexually transmitted disease (STD) clinics, emergency rooms, etc. (MMWR 1998;4Newer and better rapid tests are anticipated in 2001. These newer tests have the following advantadetect HIV-1 and HIV-2, they appear to be as accurate as standard serologic tests, they can be perfusing saliva as well as blood, results are available in 10 minutes, and they can be read by the providIntern Med 1999;131:4810; J Clin Microbiol 1999;37:3698; ASM News 2000;66:451). Initial results wOraQuick, a rapid test using saliva, in 219 seropositive persons and 779 seronegative persons showsensitivity of 100% and specificity of 99.9% compared with standard serology (8th CROI, Chicago, IFebruary 2001, Abstract 232).Saliva Test: OraSure (Epitope Co., Beaverton, Ore.), is an FDA-approved device for collecting salivaconcentrating IgG for application of EIA tests for HIV antibody. The OraSure test system consists ofspecimen collection device, the Organon Teknika Vironostika HIV-1 antibody screen, and the WBconfirmatory assay, at a cost of $24.15/test. It is available for testing in public health departments, poffices, community-based service organizations and AIDS Service organizations. OraSure testing isavailable by calling 800-Ora-Sure (800-672-7872). The test may be anonymous or confidential. Resavailable by phone or fax within 3 days. The test uses a specially treated pad which is placed betwelower cheek and gum for 2 minutes. The pad is then placed in a vial that is submitted to a lab. The aIgG obtained from saliva is far higher than in plasma and is well above the 0.5mg/L level necessarydetection of HIV antibodies. Specimens saved from 3570 subjects gave correct results compared wstandard serology in 672 of 673 (99.9%) positives and 2893 of 2897 (99%) negatives (JAMA 1997;2Potential advantages over standard serologic testing are the ease of collecting specimens, reducedbetter patient acceptance.Urine Test: Calypte HIV-1 Urine EIA is an FDA-approved screening EIA available through Seradyn In800-428-4007. This test can be administered only by a physician, and positive results require confirma standard serologic test. Reported sensitivity is 99% (88/89), specificity is 94% (49/52) (Lancet1991;337:183; Clin Chem 1999;45:1602). The supplier has included a pretest counseling form, whicbe read to and initialed by the patient prior to administration. The assay is sold as a 192-test kit at $480-test kit at $1920; these costs equal $4/test.Vaginal secretions: HIV antibodies can be detected in vaginal secretions with IgG EIA (WellcozymHIV-1&2, Gracelisa Murex Diagnostics Ltd., Darford, UK). This test is recommended by the CDC forrape, since HIV IgG antibodies are in semen (MMWR 1985;34:75S; J Clin Microbiol 1994;32:1249).Viral Detection: Other methods to establish HIV infection include techniques to detect HIV antigen, DRNA (Table 2-1). HIV-1 DNA PCR is the most sensitive and can detect 1-10 copies of HIV proviral DNone of these tests is considered superior to routine serology in terms of accuracy, but some may bpatients with confusing serologic test results, when there is a need to clarify indeterminate test resuvirologic monitoring in therapeutic trials, and for HIV detection when routine serologic tests are likelymisleading such as in patients with agammaglobulinemia, acute retroviral infection, neonatal HIV infand patients in the window following viral exposure. In most cases, confirmation of positive serologyaccomplished simply by repeat serology. The sensitivity of tests for detection of HIV varies with thedisease and test technique, but is usually reported at >99% for DNA-PCR, 90% to 95% for quantitatHIV-RNA, 95% to 100% for viral culture of peripheral blood mononuclear cells (PBMC), and 8% to 3p24 antigen detection (J Clin Microbiol 1993;31:2557; N Engl J Med 1989;321:1621; J AIDS 1990;3Infect Dis 1994;170:553; Ann Intern Med 1996;124:803). None of these tests should replace serologcircumvent the informed consent process.Table 2-1: Tests for HIV-1Assay Sensitivity CommentsRoutine 99.7% Readily available and inexpensive. Sensitivity and specificity >99.9% (MMWR 1990;39:serology Engl J Med 1988;319:961; JAMA 1991;266:2861).
    • Routine 99.7% Readily available and inexpensive. Sensitivity and specificity >99.9% (MMWR 1990;39:serology Engl J Med 1988;319:961; JAMA 1991;266:2861).Rapid test 99.9% Results are available in <10 minutes but test must be performed by a lab technician. SpSUDS [Murex 99.6%; positive tests should be confirmed. Highly sensitive; negative tests do not usuallDiagnostics, confirmation. Other rapid tests are available but are not FDA approved (Int J STD AIDSNorcross, Ga.] 1997;8:192; Vox Sang 1997;72:11).Salivary test 99.9% Salivary collection device to collect IgG for EIA and WB. Advantage is avoidance of phle(OraSure Test Sensitivity and specificity are comparable to standard serology (JAMA 1997;227:254).System)Urine test >99.9% Used for EIA test only, so positive results must be verified by serology. Must be adminis(Calypte 1) physician. Cost is low - about $4/test.PBMC culture 95% to Viral isolation by co-cultivation of patients PBMC with phytohemagglutinin (PHA)-stimul 100% PBMC with IL-2 over 28 days. Expensive and labor-intensive. May be qualitative or qua Main use of qualitative technique is viral isolation for further analysis and for HIV detect infants. Quantitative results correlate with stage: Mean titer is 20/10 6 cells in asymptoma patients and 2200/106 cells in patients with AIDS (N Engl J Med 1989;321:1621).DNA PCR >99%assay Qualitative DNA PCR is used to detect cell-associated proviral DNA; primers are comme available from Roche Laboratories. Sensitivity is >99% and and specificity is 98%. This considered sufficiently accurate for diagnosis without confimation and is not FDA-appro Intern Med 1996;124:803). Main use is for viral detection in the case of neonatal HIVand or indeterminate serologic tests.HIV RNA PCR 95% to False-positive tests in 2% to 9%; usually at low titer. Sensitivity depends on viral load th 98% assay and assumes no antiretroviral therapy. Top of Page | Next page -- Quantitative Plasma HIV RNACopyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rights reserved.* Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained in this site because no sor service can take the place of medical training, education, and experience. Consumers are cautioned that this site is not intended to provide medical aspecific medical condition they may have or treatment they may need and they are encouraged to call or see their physician or other health care provideany health related questions they may have.
    • Go to a Chapter Table of Contents Natural History and Classification Tests Disease Prevention Antiretroviral Therapy Management of Opp Infections Drugs: Guide to Information Systems Review HIV in Correc Chapter II: Laboratory Tests Contents: HIV Types and Subtypes Chest X-Ray HIV Serology PPD Skin Testing Alternative HIV Serologic Tests PAP Smears Quantitative Plasma HIV RNA Serology for Hepatitis B Virus (HBV) CD4 Cell Count Testing for Hepatitis C Virus Resistance Testing Toxoplasmosis Serology Screening Battery Cytomegalovirus Serology Complete Blood Count Glucose-6-Phosphate Dehydrogenase Levels Serum Chemistry Panel Adverse Drug Reaction Monitoring Syphilis Serology Tables Table 2-1: Test for HIV-1 Table 2-2: Comparison Between Assay Methods for Viral Load Table 2-3: Comparison of Genotypic and Phenotypic Assays Table 2-4: Letter Designations for Amino Acids Table 2-5: Resistance Mutations Table 2-6: Routine Laboratory Test in Asymptomatic Patients Table 2-7: Recommendations for Intervention Based on Results of PAP Smear Table 2-8: Tests for HCV Quantitative Plasma HIV RNA (Viral Burden)Techniques: see Table 2-2 and Table 2-3 1. HIV RNA PCR (Amplicor HIV-1 Monitor versions 1.0, and 1.5, Roche Labs; 800-526-1247). Ve is FDA approved; version 1.5 is available commercially and detects non-B subtypes. Both the 1.5 versions are available in the "standard" assay and the "ultrasensitive" assay (J Clin Microb 1999;37:110). 2. Branched chain DNA or bDNA (Quantiplex HIV RNA 3.0 assay, Bayer, 800-434-2447, formerl Version 2.0 is being phased out. 3. Nucleic acid sequence-based amplification or Nuclisens HIV-1 QT (Organon Teknika), 800-68 x152Reproducibility: Commercially available assays vary based on the lower level of detection and dynam(J Clin Microbiol 1996;34:3016; J Med Virol 1996;50:293; J Clin Microbiol 1996;34:1058; J Clin Micr1998;36:3392). Two standard deviations (95% confidence limits) with this assay are 0.3 to 0.5 log (23-fold) (J Infect Dis 1997;175:247; AIDS 1999;13:2269). This means that the 95% confidence limit fof 10,000 c/mL ranges from 3100 to 32,000 c/mL. Recent studies indicate that the viral load in asymwomen is 2-fold lower than seen in men at the same CD4 cell counts for early stage disease (Lance1998;352:1510; N Engl J Med 2001;344:270). This difference disappears with disease progressionDis 1999;180:666). Quantitative results with the Amplicor (Roche) assay are about one-half (0.3 logthose of Quantiplex version 3.0; comparitive data for the Nuclisens assay are not available (J Clin M2000;38:2837).Cost: $100 to $150 per assay (Medicare reimbursement $111 to $130)Indications: Quantitative HIV RNA is useful for diagnosing acute HIV infection, for predicting progreschronically infected patients, and for therapeutic monitoring (Ann Intern Med 1995;122:573; N Engl
    • Cost: $100 to $150 per assay (Medicare reimbursement $111 to $130)Indications: Quantitative HIV RNA is useful for diagnosing acute HIV infection, for predicting progreschronically infected patients, and for therapeutic monitoring (Ann Intern Med 1995;122:573; N Engl1996;334:426; J Infect Dis 1997;175:247). Acute HIV infection: Plasma HIV RNA levels are commonly determined to detect the acute re syndrome prior to seroconversion. Most studies show high levels of virus (10 5 to 106 c/mL). No 2% to 9% of persons without HIV infection have false-positive results, virtually always with low titers (<10,000 cells/mm3) (Ann Intern Med 1999;130:37; J Clin Microbiol 2000;38:2837; Ann I 2001;134:25). The alternative is the HIV p24 antigen assay, which is less expensive ($20 vs $ highly specific, but only 89% sensitive (Ann Intern Med 2001;134:25). Prognosis: The most comprehensive study to assess the association between viral load and history is the analysis of stored sera from the Multicenter AIDS Cohort Study (MACS), which s strong association between "set point" and rate of progression that was independent of the ba CD4 cell count (Ann Intern Med 1995;122:573; Science 1996;272:1167; J Infect Dis 1996;174 Infect Dis 1996;174:704; AIDS 1999;13:1305). Probability of transmission: The probability of HIV transmission with nearly any type of expo directly correlated with viral load (N Engl J Med 2000;342:921; J AIDS 1996;12:427; J AIDS 1 J AIDS 1999;21:120). Therapeutic Monitoring: Following initiation of therapy there is a rapid initial decline in HIV R (alpha slope), reflecting activity against free plasma HIV virions and HIV in acutely infected CD This is followed by a second decline (beta slope) that is longer in duration (months) and more degree. The latter reflects activity against HIV infected macrophages, and HIV released from o compartments, especially those trapped in follicular dendritic cells of lymph follicles. The maxim antiviral effect is expected by 4 to 6 months. Most authorities now believe that HIV RNA levels most important barometer of therapeutic response (N Engl J Med 1996;335:1091; Ann Intern M 1996;124:984). Unexpectedly low viral load: The Roche assay (RT-PCR) Version 1.0 uses primers designe for detection of clade B strains of HIV, since this is the predominant clade in the United States Europe, where HAART is used. Patients with non-clade B strains may show deceptively low p RNA levels. The bDNA assay, the Roche 1.5 version test, or the Nuclisens HIV-1QT assay wi more accurate quantitation of non-clade B strains, since these assays amplify subtypes A-G. N accurate for the non-M subtypes (N or O) or HIV-2 strains.Recommendations: Adapted from the International AIDS Society-USA (Nat Med 1996;2:625) and DHHGuidelines (MMWR 1998;47[RR-3]:38). Quality assurance: Assays on individual patients should be obtained at times of clinical stabi least 4 weeks after immunizations or intercurrent infections, and with use of the same lab and technology. Frequency: Tests should be performed at baseline (x2) followed by routine testing at 3- to 4-m intervals. With new therapy and changes in therapy, assays should be obtained at 2 to 4 week slope), 12 to 16 weeks, and at 16 to 24 weeks. An optimal response to therapy should be asso with a 1.5 to 2 log10 decrease at 4 weeks, <500 c/mL at 12 to 16 weeks, and <50 c/mL at 16 to weeks. (Authors comment: Time to viral load nadir is dependent on pretreatment viral load as potency of the regimen, compliance, pharmacology, and resistance. Patients with high baselin loads take longer to achieve suppression than those with low viral loads.) Interpretation: Changes of >50% (0.3 log10) are considered significant. Factors not measured by viral load tests: immune function, CD4 regenerative reserve, sus to antivirals, infectivity, syncytial vs nonsyncytial inducing forms and viral load in compartment than blood (eg, lymph nodes, CNS, genital secretions). Factors that increase viral load: 1. Progressive disease 2. Failing antiretroviral therapy due to inadequate potency, inadequate drug levels, nonadhere
    • Factors not measured by viral load tests: immune function, CD4 regenerative reserve, susto antivirals, infectivity, syncytial vs nonsyncytial inducing forms and viral load in compartmentthan blood (eg, lymph nodes, CNS, genital secretions).Factors that increase viral load: 1. Progressive disease 2. Failing antiretroviral therapy due to inadequate potency, inadequate drug levels, nonadhere resistance, and/or drug interactions. 3. Active infections: active TB increases viral load 5- to 160-fold (J Immunol 1996;157:1271); pneumococcal pneumonia increases viral load 3- to 5-fold. 4. Immunizations such as influenza and Pneumovax (Blood 1995;86:1082; N Engl J Med 1996;335:817; N Engl J Med 1996;334:1222).False low viral loads: 1) non-B subtypes using the Amplicor (Roche) Version 1.0; 2) HIV-2 indual HIV-1 and HIV-2 infection.Relative merit of tests: The Quantiplex version 3.0 assay has good reproducibility for viral load levels of 100 to 500,000 c/mL. The linear range for Amplicor is 50 to 75,000 c/mL for the ultrasensitive test requiring a different test for specimens with higher viral loads (J Clin Microbiol 2000;38:283 Amplicor version 1.0 is FDA approved. The Nuclisens assay has a broad dynamic range (5 3,000,000 c/mL) and can be used for HIV quantitation in non blood or on various body fluid tissue such as seminal fluid, CSF, breast milk, saliva, and vaginal fluid. (J Clin Microbiol 2000;38:1414). Table 2-2: Comparison Between Assay Methods for Viral Load Roche Bayer (formerly Chiron) Organon Contact 800-526-1247 800-434-2447 800-682-2666 x152 Technique RT-PCR bDNA Nuclisens HIV-1 QT Comparison of Results with the RT-PCR assay Results with bDNA are 50% of results Comparative results with PT-PCR results are about 2x results with bDNA with RT-PCR for the version 2.0 or using version 2.0 or 3.0. 3.0. Advantages Amplicor Version 1.0 is FDA Technician time demands are less May be used with tissue or body f approved such as genital secretions Amplifies subtypes A-G Amplifies subtypes A-G Fewer false positives compared with Chiron Greatest dynamic range Version 1.5 amplifies subtypes A-G Dynamic range Standard: (Amplicor 1.0 and 1.5) bDNA Quantiplex Version 3.0: 100 to Nuclisens HIV-1 QT: 40 to 10,000 400 to 750,000 c/mL 500,000 c/mL c/mL (depending on volume) Ultrasensitive (Ultra-Direct 1.0 and 1.5): 50 to 75,000 c/mL Subtype Version 1.0: B only A-G A-G amplified Version 1.5: A-G Specimen Amplicor - 0.2 mL 1 mL 10 µL to 2 mL volume Ultrasensitive - 0.5 mL Tubes EDTA EDTA EDTA, heparin, whole blood, any (lavender top) (lavender top) fluid, PMBC, semen, tissue etc. Requirement Separate plasma <6 hrs and freeze Separate plasma <4 hrs and freeze Separate serum or plasma <4 hrs prior to shipping at -20 oC or -70 oC prior to shipping at -20 oC or -70 oC freeze prior to shipping at -20oC o -70 oC Top of Page | Next page -- CD4 Cell Count
    • Top of Page | Next page -- CD4 Cell CountCopyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rights reserved.* Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained in this site because no sor service can take the place of medical training, education, and experience. Consumers are cautioned that this site is not intended to provide medical aspecific medical condition they may have or treatment they may need and they are encouraged to call or see their physician or other health care provideany health related questions they may have.
    • Go to a Chapter Table of Contents Natural History and Classification Tests Disease Prevention Antiretroviral Therapy Management of Opp Infections Drugs: Guide to Information Systems Review HIV in Correc Chapter II: Laboratory Tests Contents: HIV Types and Subtypes Chest X-Ray HIV Serology PPD Skin Testing Alternative HIV Serologic Tests PAP Smears Quantitative Plasma HIV RNA Serology for Hepatitis B Virus (HBV) CD4 Cell Count Testing for Hepatitis C Virus Resistance Testing Toxoplasmosis Serology Screening Battery Cytomegalovirus Serology Complete Blood Count Glucose-6-Phosphate Dehydrogenase Levels Serum Chemistry Panel Adverse Drug Reaction Monitoring Syphilis Serology Tables Table 2-1: Test for HIV-1 Table 2-2: Comparison Between Assay Methods for Viral Load Table 2-3: Comparison of Genotypic and Phenotypic Assays Table 2-4: Letter Designations for Amino Acids Table 2-5: Resistance Mutations Table 2-6: Routine Laboratory Test in Asymptomatic Patients Table 2-7: Recommendations for Intervention Based on Results of PAP Smear Table 2-8: Tests for HCV CD4 Cell CountThis is a standard test to stage the disease, formulate the differential diagnosis of patient complaints1-2), and to make therapeutic decisions regarding antiviral treatment and prophylaxis for opportunispathogens. It is also a relatively reliable indicator of prognosis that complements the viral load assaytwo assays independently predict clinical progression and survival (Ann Intern Med 1997;126:946).counts have not been found to predict outcome (N Engl J Med 1990;322:166).Return to top Technique
    • The standard method for determining CD4 cell count uses flow cytometers and hematology analyzeexpensive and require fresh blood (<18 hours old). The cost of the test ranges from $50 to $150. Analternative system that uses EIA technology is the TRAX CD4 Test Kit (J AIDS 1995;10:522). This mattractive in resource-limited areas.Normal values for most laboratories are a mean of 800 to 1050/mm 3 with a range representing twodeviations of approximately 500 to 1400/mm3 (Ann Intern Med 1993;119:55).Frequency of testing: CD4 cell count <350/mm3 - every 3 to 4 months; CD4 cell count >350/mm 36 months (Clin Infect Dis 2000;30:5); <50 cells/mm 3 optional. Frequency will vary with individualcircumstances.Factors that influence CD4 cell counts include analytical variation, seasonal and diurnal variationintercurrent illnesses, and corticosteroids. Substantial analytical variations, which account for the wiin normal values (usually about 500 to 1400/mm 3), reflect the fact that the CD4 cell count is the prodthree variables: the white blood cell count, % cells, and the % CD4 cells (cells that bear the CD4 recThere are also seasonal changes (Clin Exp Immunol 1991;86:349) and diurnal changes with lowest12:30 PM and peak values at 8:30 PM (J AIDS 1990;3:144), these variations do not clearly correspcircadian rhythm of corticosteroids. Modest decreases in the CD4 cell count have been noted with sacute infections and with major surgery. Corticosteroid administration may have a profound effect wdecreases from 900/mm 3 to less than 300/mm3 with acute administration; chronic administration haspronounced effect. (Clin Immunol Immunopathol 1983;28:101). Acute changes are probably due toredistribution of leukocytes between the peripheral circulation and the marrow, spleen, and lymph noExp Immunol 1990;80:460). Co-infection with HTLV-1 may be responsible for a deceptively high CDcount in the presence of immune suppression from HIV-1. Splenectomy may also cause deceptivelylevels. The following have minimal effect on the CD4 cell count: gender, age in adults, risk categorypsychological stress, physical stress, and pregnancy (Ann Intern Med 1993;119:55).The CD4 cell percentage is sometimes used in preference to the absolute number, since this reducevariation to one measurement (J AIDS 1989;2:114). In the AIDS Clinical Trial Group (ACTG) laborawithin-subject coefficient of variation for % CD4 was 18% compared with 25% for the CD4 cell counDis 1994;169:28). Corresponding CD4 cell counts are:CD4 Cell Count % CD4>500/mm3 >29% 3200 to 500/mm 14% to 28%<200/mm3 <14%Precautions in the use and interpretation of CD4 cell counts include the need for both clinicianspatients to be aware of the fluctuations described above. Test results that represent "milestones" fotherapeutic decisions be repeated, especially if they show values that do not correlate well with prioPrior studies show the 95% confidence ranges for a true count of 500/mm3 were 297 to 841/mm3 an337/mm3 for a count of 200/mm3 (J AIDS 1993;6:537). Deceptively high CD4 cell counts are noted iwith concurrent human T-cell leukemia virus (HTLV)-1 infection and in patients with a splenectomy,the agent of adult T cell leukemia and tropical spastic paraparesis. HTLV-1 is closely related to HTLmost serologic assays show cross reactivity, but only HTLV-1 causes deceptively high CD4 cell couSerologic studies in the United States show HTLV-1/2 infection rates of 7% to 12% in injection drug2% to 10% in commercial sex workers (N Engl J Med 1990;326:375; JAMA 1990;263:60); 80% to 9these are HTLV-2 in both populations. High rates of concurrent HIV and HTLV-1 have been reporte
    • with concurrent human T-cell leukemia virus (HTLV)-1 infection and in patients with a splenectomy,the agent of adult T cell leukemia and tropical spastic paraparesis. HTLV-1 is closely related to HTLmost serologic assays show cross reactivity, but only HTLV-1 causes deceptively high CD4 cell couSerologic studies in the United States show HTLV-1/2 infection rates of 7% to 12% in injection drug2% to 10% in commercial sex workers (N Engl J Med 1990;326:375; JAMA 1990;263:60); 80% to 9these are HTLV-2 in both populations. High rates of concurrent HIV and HTLV-1 have been reporte(JAMA 1994;271:353) and Haiti (J Clin Microbiol 1995;33:1735). Analysis of patients with co-infectiosuggests that CD4 cell counts were 80% to 180% higher than controls for comparable levels ofimmunosuppression (JAMA 1994;271:353).The CD4 cell count may be used as a surrogate marker of HIV infection in patients for whom seroloare delayed or in patients who have refused the test. There are relatively few conditions associatedprofound depletion of CD4 cell counts in patients with classic AIDS-indicator conditions included in tdifferential diagnosis. The median CD4 cell count at the time of an AIDS-defining diagnosis is 60/mm<10% have an AIDS-defining diagnosis with a CD4 cell count >200/mm3 (Am J Epidemiol 1995;141Thus, a patient with a CD4 cell count of 800/mm 3 with thrush, possible PCP, or cryptococcal meningunlikely to have HIV infection. The total cell count may serve in a similar fashion, is readily availableadvocated by the World Health Organization (WHO) in settings where a CD4 cell count is not availatotal cell count of <1000/mL is strongly predictive of a CD4 cell count <200/mm 3.Return to top CD4 RepertoireProgressive immunodeficiency in HIV infection is associated with both quantitative and qualitative cCD4 cells. There are two major categories of CD4 cells: naïve cells and memory cells. In early life, aare naïve and express the isoform of CD45RA +. Memory cells (CD45RA- ) represent the componentcell repertoire that has been activated by exposure to antigens. These are the CD4 cells with specifmost opportunistic infections such as P. carinii, cytomegalovirus, and Toxoplasma gondii. It is the dthese cells that accounts for the inability to respond to recall antigens, a defect noted relatively earlycourse of HIV infection. Studies of HIV-infected patients show a preferential decline in naïve cells. Wtherapy using protease inhibitors, there is a three-phase component to the CD4 rebound. The initialis due primarily to redistribution of CD4 cells from lymphatic sites. The second phase is characterizeinflux of CD4 memory cells with reduced T cell activation and improved response to recall antigens.third phase there is an increase in naïve cells following at least 12 weeks of HAART (Nat Med 1997Science 1997;277:112). By 6 months, the CD4 repertoire is diverse; the competence of these cellsevidenced by favorable control of selected chronic infections such as cryptosporidiosis, microsporidMolluscum contagiosum; the ability to safely discontinue maintenance therapy for dissemminated MCMV; and the ability to safely discontinue PCP and MAC prophylaxis in responders. Nevertheless, spatients with immune reconstitution have deficits in CTL responses to specific antigens that may resor relapses in CMV retinitis despite CD4 cell counts >300/mm 3 (Hopkins HIV Report 2000;12:3; 7thSan Francisco, Calif. February 2000, Abstracts 272, 580, 581; J Infect Dis 2001;183:1285).Idiopathic CD4 lymphocytopenia (ICL) is a syndrome characterized by a low CD4 cell count thatunexplained by HIV infection or other medical conditions. Criteria for the case definition are: 1) CD4less than 300/mm3 or a CD4 percent less than 20% on two or more measurements; 2) lack of laboraevidence of HIV infection; and 3) absence of alternative explanation for the CD4 cell lymphopenia. Tdecreases in CD4 cells may occur with infections due to tuberculosis, M. avium, hepatitis B, EBV,toxoplasmosis, cryptococcosis, and CMV (Chest 1994;105:1335; Eur J Med 1993;2:509; Am J Med1996;312:240). The diagnosis of ICL requires persistence of the deficit. Through May 1993, there wadults and 14 children reported to the CDC with ICL. Several conclusions can be drawn from the exwith these patients: 1) they lack risk factors for HIV infection; 2) there is no evidence of an infectiousbased on clustering or contact evaluations; 3) these patients often have the same opportunistic infenoted with HIV infection, though there are some differences including higher rates of extrapulmonarcryptococcosis; 4) CD4 cell counts tend to remain stable; and 5) the prognosis is relatively good (La1992;340:273; N Engl J Med 1993;328:373; N Engl J Med 1993;328:380; N Engl J Med 1993;328:3Engl J Med 1993;328:393). Cases of this syndrome should be reported to local/state health departmrather than the direct reporting to the CDC that was originally advocated.
    • based on clustering or contact evaluations; 3) these patients often have the same opportunistic infenoted with HIV infection, though there are some differences including higher rates of extrapulmonarcryptococcosis; 4) CD4 cell counts tend to remain stable; and 5) the prognosis is relatively good (La1992;340:273; N Engl J Med 1993;328:373; N Engl J Med 1993;328:380; N Engl J Med 1993;328:3Engl J Med 1993;328:393). Cases of this syndrome should be reported to local/state health departmrather than the direct reporting to the CDC that was originally advocated. Top of Page | Next page -- Resistance TestingCopyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rights reserved.* Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained in this site because no sor service can take the place of medical training, education, and experience. Consumers are cautioned that this site is not intended to provide medical aspecific medical condition they may have or treatment they may need and they are encouraged to call or see their physician or other health care provideany health related questions they may have.
    • Go to a Chapter Table of Contents Natural History and Classification Tests Disease Prevention Antiretroviral Therapy Management of Opp Infections Drugs: Guide to Information Systems Review HIV in Correc Chapter II: Laboratory Tests Contents: HIV Types and Subtypes Chest X-Ray HIV Serology PPD Skin Testing Alternative HIV Serologic Tests PAP Smears Quantitative Plasma HIV RNA Serology for Hepatitis B Virus (HBV) CD4 Cell Count Testing for Hepatitis C Virus Resistance Testing Toxoplasmosis Serology Screening Battery Cytomegalovirus Serology Complete Blood Count Glucose-6-Phosphate Dehydrogenase Levels Serum Chemistry Panel Adverse Drug Reaction Monitoring Syphilis Serology Tables Table 2-1: Test for HIV-1 Table 2-2: Comparison Between Assay Methods for Viral Load Table 2-3: Comparison of Genotypic and Phenotypic Assays Table 2-4: Letter Designations for Amino Acids Table 2-5: Resistance Mutations Table 2-6: Routine Laboratory Test in Asymptomatic Patients Table 2-7: Recommendations for Intervention Based on Results of PAP Smear Table 2-8: Tests for HCV Resistance TestingResistance testing is an in vitro method to measure resistance of HIV to antiretroviral agents. Resistesting can aid in antiretroviral drug selection but has certain limitations: 1) resistance assays measuthe dominant species at the time the test is performed; resistant variants that comprise less than 20total viral population and species in "sequestered havens" (CNS, latent CD4 cells, genital tract, etc.)detected; 2) there must be a sufficient viral load to do the test, usually >500 to 1000 c/mL; 3) genotyassays are often difficult to interpret, since multiple mutations are required for antiretroviral agents o3TC and non-nucleoside reverse transcriptase inhibitors (NNRTIs). Phenotypic assays may be difficinterpret due to the fact that thresholds used to define susceptibility may not necessarily reflect theappropriate drug concentrations. As a result of these limitations: Resistance testing most reliably identifies drugs that should be avoided, but not necessarily th that are most likely to be active. Testing should be performed in the presence of the antiretroviral agents in question, since discontinuation of therapy often results in the proliferation of wild type virus that may deceptive suggest susceptibility. The time between discontinuation of HAART and the shift from resistan to wild type virus is usually 2 to 8 weeks, though there is considerable variation. The usual recommendation is a 2-week allowance. Interpretation of results in patients who have received prior antiretroviral agents is difficult. Re previously used drugs may be present even if resistance assays indicate susceptibility, so tha drug history and outcome are important factors in regimen selection. A viral load of 500 to 1000 c/mL is usually required. Results are most accurate with failure of early regimens.Indications (DHHS Guidelines February 5, 2001, available at http://www.hivatis.org) Recommended: Chronically infected patient receiving antiretroviral therapy with: 1) failure to decrease viral load >0.5 to 0.7 log10 c/mL by 4 weeks; 2) failure to decrease viral load >1 log10
    • Indications (DHHS Guidelines February 5, 2001, available at http://www.hivatis.org) Recommended: Chronically infected patient receiving antiretroviral therapy with: 1) failure to decrease viral load >0.5 to 0.7 log10 c/mL by 4 weeks; 2) failure to decrease viral load >1 log10 c/mL by 8 weeks; or 3) viral load >1000 c/mL after 16 to 24 weeks. Consider: Acute HIV syndrome Not recommended: 1) in treatment-naïve patient with chronic HIV infection; 2) in patient who not received antiretroviral agents for >2 weeks; or 3) in patient with viral load <1000 c/mL.Return to top Test MethodsThere are two types of tests: genotypic and phenotypic assays. These are compared in Table 2-3.Table 2-3: Comparison of Genotypic and Phenotypic AssaysGenotypic AssaysAdvantages Disadvantages Detect resistance only in dominant species (>20%)Less expensive ($300 to $480/test)* Interpretation requires knowledge of mutational changes, egShort turn-around: 1 to 2 weeks Technician experience influences results.May detect presence of resistance mutations beforethey have resulted in phenotypic resistance May show discrepancy with phenotype Require viral load >1000 c/mLPhenotypic AssaysAdvantages DisadvantagesInterpretation more analogous to resistance testing of More expensive (usually $800 to $1000)bacteria. Longer delay in reporting: 2 to 3 weeksAssesses total effect, including mutations, mutationalinteractions. Thresholds to define susceptibility are arbitrary and nonstan and do not always reflect achievable drug concentrations.Reproducibility is good. Detect resistance only in dominant species (>20%).Advantage over genotype when there are multiplemutations Require viral load >500 to 1000 c/mL.*Cost: Medicare/Medicaid reimbursement per HFCA announcement January 8, 2001 - Genotype test $355.78 (code 8phenotype test $675.29 (1st 10, code 8703), each additional drug $36.02 (code 8704).Table 2-4: LetterDesignations for AminoAcids* A Alanine
    • phenotype test $675.29 (1st 10, code 8703), each additional drug $36.02 (code 8704). A Alanine C Cytosine D Aspartic acid E Glutamic acid F Phenylalanine G Glycine H Histidine I Isoleucine K Lysine L Leucine M Methionine N Asparagine P Proline Q Glutamine R Arginine S Serine T Threonine V Valine W Tryptophan Y Tyrosine*Amino acids and corresponding single-letter codes used in describing genotypes.Return to top Genotypic Assays
    • These assays are available from multiple commercial suppliers, and there are also a number of "hombrews." Assays vary considerably based on cost, the number of mutations tested, and simplicity andof reporting. The methodology involves: 1) amplication of the reverse transcriptase (RT), protease (or both by RT PCR; 2) DNA sequencing of amplicons generated for the dominant species (mutationlimited to those present in >20% of plasma virions); 3) reporting of mutations for each gene using aletter-number-letter standard, in which the first letter indicates the amino acid at the designated codowild type virus, the number is the codon, and the second letter indicates the amino acid substitutedmutation (Table 2-4). Thus, the RT mutation K103N indicates that asparagine (N) has substituted fo(K) on codon 103. The table indicates the amino acids and corresponding letter codes used to descmutations in genotype analyses. Updated information on resistance testing can be obtained athttp://hiv-web.lanl.gov. Table 2-5: Resistance Mutations Adapted from Hirsch et al, JAMA 2000;283:2417 Drug Codon Mutations Comment Nucleosides and Nucleotides AZT 41, 67, 70, 210, 215, 219 Mutations are "TAMS"* - reduce susceptibility to AZT ABC 3TC 184 184 - high level 3TC resistance, increases activity of and tenofovir ddC 69, 65, 184 ddI 65, 74, 184 Presence of either 74 or 65 associated with intermed resistance to ddI. High-level resistance associated w presence of both mutations. 184 causes low-level res d4T 41, 67, 70, 75, 210, 215, 219 The d4T specific mutation at 75 is seen mostly in vitr resistance depends on number of TAMS, which redu susceptibility of d4T, AZT, and ABC. ABC 41, 65, 67, 70, 74, 115, 184, 210, Resistance depends on number of TAMs. Virus with 215, 219 and 3 or more TAMs is generally resistant to ABC. AB for mutations that may confer cross-resistance to 3TC Mutlinucleoside 62, 75, 77, 116, 151, Occurs with or without TAMs. Confers resistance to a resistance - A but not to tenofovir. Mutlinucleoside 41, 62, 67, 69 (insertion) 70, 210, Requires TAMs. Confers resistance to all NRTIs and resistance - B 215, 219 but not to DAPD. NNRTIs NVP 100, 103, 106, 108, 181, 188, 190, Y181C is favored mutation with NVP, unless combine 230 AZT, in which case K103N is favored. DLV 103, 181, 230, 236, EFV 100, 103, 108, 188L, 190, 225, 230 Sensitive in vitro to 181 mutants; resistance with 188 188C or 188H. Protease Inhibitors (PIs) Drug Primary Secondary Comment IDV 46, 82 10, 20, 24, 63, At least 3 mutations required for resistance (>4x decr 64, 82, 84, 90 susceptibility) NFV 30, 90, 35, 36, 46, 71, D30N most common mutation: no PI cross-resistance 88, occurs in some, leading to greater PI cross-resistanc RTV 82, 8, 10, 20, 33, Cross resistance with IDV common 36, 46, 54, 63,
    • RTV 82, 8, 10, 20, 33, Cross resistance with IDV common 36, 46, 54, 63, 71, 84, 90 SQV 48, 90 10, 24, 30, 46, 90 develops 1st, then 48; Codon 48 mutation unique 54, 63, 64, 71, confers PI cross-resistance. 73, 77, 81, 84, 88, APV 50, 84 10, 32, 46, 47, 50 not associated with cross-resistance. 54 LPV - 10, 20, 24, 46, Resistance correlates with number mutations. Minima 53, 63, 71, 82, available on PI mutations following LPV/RTV failure. 84, 90 The distinction between primary and secondary mutations has been eliminated for NRTIs and NNRTIs by the Interna AIDS Society Expert Committee; this distinction has been retained for PIs. Primary mutations-usually develop first; associated with decreased drug binding. Secondary mutations-also contribute to drug resistance; may affect drug binding in vitro less than primary mutatio * Evolving data suggest cross-resistance between AZT with d4T and ABC ascribed to thymidine analog mutations (T induced by exposure to AZT or d4T.Return to top Phenotypic AssaysPhenotypic analysis involves insertion of the RT and protease genes from the patients strain into alaboratory clone by cloning or recombination. Replication is monitored at various drug concentrationcompared to a reference wild type virus. This assay is comparable to conventional in vitro tests ofantimicrobial sensitivity, in which the microbe is grown in serial dilutions of antiviral agents. Resultsreported as the IC50 for the test strain relative to that of a reference or wild type strain. The interpretpreviously based on a fixed ratio such as 4x to define resistance, meaning resistance is 4-fold greatthat of the reference strain. The newer method is to individualize by drug. For Virco, the fold changedefine resistance are: zidovudine (AZT) - 4.0, lamivudine (3TC) - 4.5, didanosine (ddI) - 3.5, zalcitab- 3.5, stavudine (d4T) - 3.0, abacavir (ABC) - 3.0, nevirapine (NVP) - 8.0, delavirdine (DLV) - 10.0, e(EFV) - 6.0, indinavir (IDV) - 3.0, ritonavir (RTV) - 3.5, nelfinavir (NFV) - 4.0, saquinavir (SQV) - 2.5amprenavir (APV) - 2.5.Virtual phenotype is a prediction of the phenotype of the test strain based on genotypic analysis. Thmutational pattern of the test strain is compared with results of phenotypic assay results with strainssimilar mutations from a databank of >55,000 HIV isolates. Top of Page | Next page -- Screening BatteryCopyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rights reserved.* Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained in this site because no sor service can take the place of medical training, education, and experience. Consumers are cautioned that this site is not intended to provide medical aspecific medical condition they may have or treatment they may need and they are encouraged to call or see their physician or other health care provideany health related questions they may have.
    • Go to a Chapter Table of Contents Natural History and Classification Tests Disease Prevention Antiretroviral Therapy Management of Opp Infections Drugs: Guide to Information Systems Review HIV in Correc Chapter II: Laboratory Tests Contents: HIV Types and Subtypes Chest X-Ray HIV Serology PPD Skin Testing Alternative HIV Serologic Tests PAP Smears Quantitative Plasma HIV RNA Serology for Hepatitis B Virus (HBV) CD4 Cell Count Testing for Hepatitis C Virus Resistance Testing Toxoplasmosis Serology Screening Battery Cytomegalovirus Serology Complete Blood Count Glucose-6-Phosphate Dehydrogenase Levels Serum Chemistry Panel Adverse Drug Reaction Monitoring Syphilis Serology Tables Table 2-1: Test for HIV-1 Table 2-2: Comparison Between Assay Methods for Viral Load Table 2-3: Comparison of Genotypic and Phenotypic Assays Table 2-4: Letter Designations for Amino Acids Table 2-5: Resistance Mutations Table 2-6: Routine Laboratory Test in Asymptomatic Patients Table 2-7: Recommendations for Intervention Based on Results of PAP Smear Table 2-8: Tests for HCV Screening BatteryThe usual screening battery advocated for patients with established HIV infection is summarized in(Clin Infect Dis 1995;21[suppl1]:S13). Complete Blood CountThe CBC is especially important in patients with HIV infection since anemia, leukopenia, lymphopenthrombocytopenia are found in 30% to 40% of patients (J AIDS 1994;7:1134). The CBC should be r3 to 6 month intervals, in part because this is a necessary component of monitoring the CD4 cell cofrequent testing is recommended in patients with symptoms suggesting marrow suppression, thosemarrow-suppressing drugs such as AZT, and those with marginal or low counts. Serum Chemistry PanelThis panel is of limited value in a general health screen (Ann Intern Med 1987;106:403) but is commadvocated in the initial evaluation of HIV infection due to high rates of hepatitis in patients at risk forcan be used to obtain baseline values in patients who are also likely to have multisystem disease, abaseline test in patients who receive multiple drugs that are potentially hepatotoxic. Studies of HIV-ipatients have shown that up to 75% have abnormal liver function tests, 20% have severe abnormalLFTs, and about half have elevated lactic dehydrogenase (LDH) levels (J AIDS 1994;7:1134). Syphilis Serology
    • The usual screening test (VDRL or RPR) should be performed at baseline and annually thereafter drates of co-infection (MMWR 1988;37:600). Up to 6% of patients with HIV infection have biologicfalse-positive (BFP) screening tests. Risk factors for BFP results include injection drug use, pregnanHIV infection (Clin Infect Dis 1994;19:1040; J Infect Dis 1992;165:1124; J AIDS 1994;7:1134; Am J1995;99:55). False-negative tests have been reported in patients with HIV infection (J Infect Dis1990;162:862; AIDS 1991;5:419; J Infect Dis 1992;165:1020), but these are rare (Ann Intern Med1990;113:872). The CDC suggest that both treponemal and non-treponemal test should be interpretusual manner" (MMWR 1998;47[RR-1]:38). A lumbar puncture is recommended for patients with ea(<1 year) when it is accompanied by neurologic signs or symptoms, when it is not treated with the sregimen of 2.4 million units of benzathine penicillin, and with therapeutic failures, and in all patientssyphilis regardless of the clinical findings (MMWR 1998;47[RR-1]:39), CSF interpretation may be coby the presence of HIV-associated abnormalities of CSF, including mononuclear cells and elevatedRelapse is common even with recommended therapy, so follow-up VDRL titers are advised at 3, 6,24 months for primary and secondary syphilis, and every 6 months thereafter until negative (MMWR1998;47[RR-1]:39). Top of Page | Next page -- Chest X-RayCopyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rights reserved.* Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained in this site because no sor service can take the place of medical training, education, and experience. Consumers are cautioned that this site is not intended to provide medical aspecific medical condition they may have or treatment they may need and they are encouraged to call or see their physician or other health care provideany health related questions they may have.
    • Go to a Chapter Table of Contents Natural History and Classification Tests Disease Prevention Antiretroviral Therapy Management of Opp Infections Drugs: Guide to Information Systems Review HIV in Correc Chapter II: Laboratory Tests Contents: HIV Types and Subtypes Chest X-Ray HIV Serology PPD Skin Testing Alternative HIV Serologic Tests PAP Smears Quantitative Plasma HIV RNA Serology for Hepatitis B Virus (HBV) CD4 Cell Count Testing for Hepatitis C Virus Resistance Testing Toxoplasmosis Serology Screening Battery Cytomegalovirus Serology Complete Blood Count Glucose-6-Phosphate Dehydrogenase Levels Serum Chemistry Panel Adverse Drug Reaction Monitoring Syphilis Serology Tables Table 2-1: Test for HIV-1 Table 2-2: Comparison Between Assay Methods for Viral Load Table 2-3: Comparison of Genotypic and Phenotypic Assays Table 2-4: Letter Designations for Amino Acids Table 2-5: Resistance Mutations Table 2-6: Routine Laboratory Test in Asymptomatic Patients Table 2-7: Recommendations for Intervention Based on Results of PAP Smear Table 2-8: Tests for HCV Chest X-rayA routine chest x-ray is recommended by the CDC (MMWR 1986;35:448), both for detection of asymtuberculosis and as a baseline for patients who are at high risk for pulmonary disease. However, inlongitudinal study of 1065 patients at various stages of HIV infection, routine x-rays performed at 0,12 months (Arch Intern Med 1996;156:191) detected an abnormality in only 123 (2%) of 5263 x-raysthe asymptomatic patients had evidence of active tuberculosis. Only one of 82 with a positive PPD habnormality on x-ray. The authors concluded that routine chest x-rays in HIV-infected patients with nPPD skin tests are not warranted. DHHS Guidelines recommend an x-ray "when clinically indicated"1998;47[RR-1]:38).Table 2-6: Routine Laboratory Tests in Asymptomatic PatientsTest Cost* Frequency and CommentHIV serology $30 to Repeat test for patients with positive test results and: 1) no confirmation available; 2) de $60 commonly accepted risk factors; 3) test done with techniques other than standard serolo other reason for concern such as undetectable viral load and normal CD4 cell count. Re for indeterminate results at 3 to 6 months.CBC $6 to Repeat at 3 to 6 months, more frequently for low values and with administration of marro $8 drugs.VDRL or RPR $5 to Repeat annually. $16CD4 cell count and $60 to Repeat every 3 to 6 months, and repeat for results that represent "milestones" for thera% $150 decisions (antiretroviral therapy and prophylaxis for opportunistic pathogens), and with are inconsistent with prior trends. Routine testing when counts are <50/mm 3 is of minim except for monitoring response to antiretroviral therapy.Chest x-ray $40 to Indicated for symptoms and signs suggesting pulmonary disease or newly detected pos $140
    • Serum chemistries $10 to Repeat annually or more frequently in patients with abnormal results and with administr $15 hepatotoxic or nephrotoxic drugs.PAP smears $25 to Repeat at 6 months and then annually if results are normal. Results reported as "inadeq $40 should be repeated. Refer to a gynecologist for results showing atypia or greater on the scale (see PAP Smears).PPD skin test $1 Repeat annually in previously PPD-negative patients who have risk for tuberculosis.Hepatitis serology $10 to Screen for vaccine candidates: anti-HBs or anti-HBc (see Serology for Hepatitis Viruses(see comments) $15 hepatitis A virus (HAV) vaccine candidates: test anti-HAV (IgG) $40 to Abnormal liver function tests: HBsAg $60 All patients: anti-hepatitis C virus (HCV)CMV IgG $10 to Sometimes advocated for low-risk patients; seroprevalence in United States adults is 50(optional - see $15 and for HIV-infected patients is >90%.comments)Toxoplasmosis $12 to Screen all patients and repeat in seronegatives if: 1) CD4 cell count is <100/mm3 and pserology IgG (see $15 not take trimethoprim-sulfamethoxazole (TMP-SMX) for P. carinii prophylaxis, and 2) sycomments) suggest toxoplasmosis encephalitis. Agglutination assays for IgG are preferred. IgM is nG6-PD (optional - $14 to Test: 1) susceptible hosts: primarily men (X-linked) with the following ancestry: African-Asee comment) $20 Italian, Sephardic Jew, Arabs, and those from India and Southeast Asia; 2) those receiv drugs, especially dapsone and primaquine; and 3) those with typical symptoms of G6-P deficiency with testing following recovery (see Glucose-6-Phosphate Dehydrogenase Le Some authorities recommend screening all patients.Fasting lipid profile $20 to Therapeutic monitoring recommended for patients receiving antiretroviral regimens that $40 PI or NNRTI; consider at baseline and at 3 to 4 months with subsequent measurements initial results and risks.* Common charges are based on survey of five laboratories. Top of Page | Next page -- PPD Skin TestingCopyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rights reserved.* Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained in this site because no sor service can take the place of medical training, education, and experience. Consumers are cautioned that this site is not intended to provide medical aspecific medical condition they may have or treatment they may need and they are encouraged to call or see their physician or other health care provideany health related questions they may have.
    • Go to a Chapter Table of Contents Natural History and Classification Tests Disease Prevention Antiretroviral Therapy Management of Opp Infections Drugs: Guide to Information Systems Review HIV in Correc Chapter II: Laboratory Tests Contents: HIV Types and Subtypes Chest X-Ray HIV Serology PPD Skin Testing Alternative HIV Serologic Tests PAP Smears Quantitative Plasma HIV RNA Serology for Hepatitis B Virus (HBV) CD4 Cell Count Testing for Hepatitis C Virus Resistance Testing Toxoplasmosis Serology Screening Battery Cytomegalovirus Serology Complete Blood Count Glucose-6-Phosphate Dehydrogenase Levels Serum Chemistry Panel Adverse Drug Reaction Monitoring Syphilis Serology Tables Table 2-1: Test for HIV-1 Table 2-2: Comparison Between Assay Methods for Viral Load Table 2-3: Comparison of Genotypic and Phenotypic Assays Table 2-4: Letter Designations for Amino Acids Table 2-5: Resistance Mutations Table 2-6: Routine Laboratory Test in Asymptomatic Patients Table 2-7: Recommendations for Intervention Based on Results of PAP Smear Table 2-8: Tests for HCV PPD Skin TestingThe CDC recommends the Mantoux-method TST (Tuberculin Skin Test), using 5 TU of PPD, for HIpatients who have not had a prior positive test. TST should be repeated annually if initial test(s) wernegative and if the patient belongs to a population with a high risk of tuberculosis (eg, residents of pjails, injection drug users, and homeless individuals). Some authorities recommend repeat TST folloimmune reconstitution (MMWR 1998;47[RR-20]:37). Induration of >5 mm constitutes a positive test Top of Page | Next page -- PAP SmearsCopyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rights reserved.* Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained in this site because no sor service can take the place of medical training, education, and experience. Consumers are cautioned that this site is not intended to provide medical aspecific medical condition they may have or treatment they may need and they are encouraged to call or see their physician or other health care provideany health related questions they may have.
    • Go to a Chapter Table of Contents Natural History and Classification Tests Disease Prevention Antiretroviral Therapy Management of Opp Infections Drugs: Guide to Information Systems Review HIV in Correc Chapter II: Laboratory Tests Contents: HIV Types and Subtypes Chest X-Ray HIV Serology PPD Skin Testing Alternative HIV Serologic Tests PAP Smears Quantitative Plasma HIV RNA Serology for Hepatitis B Virus (HBV) CD4 Cell Count Testing for Hepatitis C Virus Resistance Testing Toxoplasmosis Serology Screening Battery Cytomegalovirus Serology Complete Blood Count Glucose-6-Phosphate Dehydrogenase Levels Serum Chemistry Panel Adverse Drug Reaction Monitoring Syphilis Serology Tables Table 2-1: Test for HIV-1 Table 2-2: Comparison Between Assay Methods for Viral Load Table 2-3: Comparison of Genotypic and Phenotypic Assays Table 2-4: Letter Designations for Amino Acids Table 2-5: Resistance Mutations Table 2-6: Routine Laboratory Test in Asymptomatic Patients Table 2-7: Recommendations for Intervention Based on Results of PAP Smear Table 2-8: Tests for HCV PAP SmearsThe CDC and the Agency for Health Care Policy and Research (AHCPR) recommend that a gynecoevaluation with pelvic exam and PAP smear be performed at baseline, repeated at 6 months and anthereafter (MMWR 1998:47[RR-1]:98; JAMA 1994;271:1866; MMWR 1999;48[RR-10]:31), with manaccording to guidelines in Table 2-7. More aggressive testing is recommended because of a severaincrease in rates of SIL (33% to 45% HIV+ vs 7% to 14% HIV-) and a 1.7-fold increase in rates of cecancer in young women with HIV (Arch Pediatr Adolesc Med 2000;154:127; Obstet Gynecol Clin N1996;23:861). Severity and frequency of cervical dysplasia increases with progressive immune comThere is a strong association between HIV infection and detectable and persistant HPV infection; thassociation increases with progressive immunosuppression (Clin Infect Dis 1995;21[suppl 1]:S121;Med 1997;337:1343).Return to top Method
    • The cervix is scraped circumflexually using an Ayer spatula or a curved brush; a sample from the pofornix or the "vaginal pool" may also be included. The endocervical sample is taken with a saline-mocotton-tipped applicator or straight ectocervical brush that is rolled on a slide and immediately fixedether plus 95% ethyl alcohol or 95% ethyl alcohol alone. The yield is 7-fold higher with the brush speImportant steps in obtaining an adequate sample: 1. Collect Pap prior to bimanual exam. 2. Avoid contaminating sample with lubricant. 3. Obtain Pap before samples for STD testing. 4. If large amounts of vaginal discharge are present, carefully remove with large swab before obt Pap. 5. Obtain ectocervical sample before endocervical sample. 6. Small amounts of blood will not interfere with cytologic sampling but if patient is bleeding more Pap should be deferred. 7. Collected material should be applied uniformly to a slide, without clumping, and should be rapi to avoid air-drying; if spray fixatives are used, the spray should be held at least 10 inches awa slide to prevent disruption of cells by propellant.When performing speculum exam, if an ulcerative or exophytic lesion suspicious for invasive cancethe patient should be referred for possible biopsy.Newer methods of cytologic evaluation using liquid-based collection and thin-layer processing may esensitivity but have not yet been evaluated in HIV-infected women.Table 2-7: Recommendations for Intervention Based on Results of PAP SmearPAP ManagementSevere inflammation Evaluate for infection; repeat PAP, preferably within 2 to 3 monthsAtypia, atypical squamous cells of Follow-up PAP without colposcopy every 4 to 6 months x 2 years until tundetermined significance (ASCUS) negative; if second report of ASCUS - perform colposcopy.Low-grade squamous intraepithelial lesion Colposcopy + biopsy or follow with PAP smear every 4 to 6 months wit(LSIL) colposcopy and biopsy if repeat smears are abnormal.High-grade squamous intraepithelia lesion Colposcopy with biopsy(HSIL) (carcinoma in situ)Invasive carcinoma Colposcopy with biopsy or conization; treat with surgery or radiation Top of Page | Next page -- Serology for Hepatitis B VirusCopyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rights reserved.* Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained in this site because no sor service can take the place of medical training, education, and experience. Consumers are cautioned that this site is not intended to provide medical aspecific medical condition they may have or treatment they may need and they are encouraged to call or see their physician or other health care provideany health related questions they may have.
    • Go to a Chapter Table of Contents Natural History and Classification Tests Disease Prevention Antiretroviral Therapy Management of Opp Infections Drugs: Guide to Information Systems Review HIV in Correc Chapter II: Laboratory Tests Contents: HIV Types and Subtypes Chest X-Ray HIV Serology PPD Skin Testing Alternative HIV Serologic Tests PAP Smears Quantitative Plasma HIV RNA Serology for Hepatitis B Virus (HBV) CD4 Cell Count Testing for Hepatitis C Virus Resistance Testing Toxoplasmosis Serology Screening Battery Cytomegalovirus Serology Complete Blood Count Glucose-6-Phosphate Dehydrogenase Levels Serum Chemistry Panel Adverse Drug Reaction Monitoring Syphilis Serology Tables Table 2-1: Test for HIV-1 Table 2-2: Comparison Between Assay Methods for Viral Load Table 2-3: Comparison of Genotypic and Phenotypic Assays Table 2-4: Letter Designations for Amino Acids Table 2-5: Resistance Mutations Table 2-6: Routine Laboratory Test in Asymptomatic Patients Table 2-7: Recommendations for Intervention Based on Results of PAP Smear Table 2-8: Tests for HCV Serology for Hepatitis B Virus (HBV)United States Public Health Service and Infectious Diseases Society of America (USPHS/IDSA) Gurecommend screening for hepatitis B core antibody (anti-HBc) (MMWR 1999;48[RR-10]:41) with HBvaccination of those who are susceptible. Antibody screening is advocated for high-risk populationsthe expense of unnecessary vaccination (MMWR 1991;40[RR-13]:1). HBV seroprevalence is 35% tgay men, 60% to 80% for injection drug users, 60% to 80% for hemophiliacs, 5% to 20% for heteroswith multiple partners, and 3% to 14% for the general population. The CDC recommends post-vacciserology with anti-HBs in patients with HIV infection at 1 to 6 months after the third dose of vaccinean antigenic response. HIV-infected patients with abnormal liver function tests should be tested for cviral hepatitis using a combination of HBV surface antigen (HBsAg) and hepatitis C antibody (anti-Hoccasional false negative serology with low CD4 cell counts. Top of Page | Next page -- Testing for Hepatitis C VirusCopyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rights reserved.* Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained in this site because no sor service can take the place of medical training, education, and experience. Consumers are cautioned that this site is not intended to provide medical aspecific medical condition they may have or treatment they may need and they are encouraged to call or see their physician or other health care provideany health related questions they may have.
    • Go to a Chapter Table of Contents Natural History and Classification Tests Disease Prevention Antiretroviral Therapy Management of Opp Infections Drugs: Guide to Information Systems Review HIV in Correc Chapter II: Laboratory Tests Contents: HIV Types and Subtypes Chest X-Ray HIV Serology PPD Skin Testing Alternative HIV Serologic Tests PAP Smears Quantitative Plasma HIV RNA Serology for Hepatitis B Virus (HBV) CD4 Cell Count Testing for Hepatitis C Virus Resistance Testing Toxoplasmosis Serology Screening Battery Cytomegalovirus Serology Complete Blood Count Glucose-6-Phosphate Dehydrogenase Levels Serum Chemistry Panel Adverse Drug Reaction Monitoring Syphilis Serology Tables Table 2-1: Test for HIV-1 Table 2-2: Comparison Between Assay Methods for Viral Load Table 2-3: Comparison of Genotypic and Phenotypic Assays Table 2-4: Letter Designations for Amino Acids Table 2-5: Resistance Mutations Table 2-6: Routine Laboratory Test in Asymptomatic Patients Table 2-7: Recommendations for Intervention Based on Results of PAP Smear Table 2-8: Tests for HCV Testing for HCVUSPHS/IDSA Guidelines recommend that all HIV-infected persons should be tested for HCV infectiothe EIA screening assay for anti-HCV antibodies; positive tests should be confirmed by either the reimmunoblot assay (RIBA) or by RT-PCR for HCV RNA (MMWR 1999;48[RR-10]:33). The only testby the FDA for the diagnosis of HCV is anti-HCV which detects >97% of infected persons but doesdistinguish acute, chronic, or resolved infection and has a low predictive value in low-prevalence po(Hepatology 1997;26:435). Supplemental antibody testing with RIBA or qualitative RT-PCR for HCVadvocated to confirm the diagnosis. However, HCV RNA assays (quantitative and qualitative) are reconfirm chronic hepatitis C infection. Serologic tests for anti-HCV may be negative with acute HCV iand with severe immunosuppression (CD4 cell count <100/mm 3); HCV RNA may be useful in theseQuantitative HCV RNA assays are not FDA approved, but are widely available using RT-PCR or bDtechnology. These tests show a threshold of detection of 100 to 1000 c/mL, and they are positive in85% of persons with anti-HCV and >95% of persons with acute or chronic hepatitis C. Rigorous quais necessary for these assays in terms of specimen preparation for laboratory submission. This testalanine aminotransferase (ALT) levels are useful in determining candidates for treatment; they mayin judging response to treatment. Genotype assay identifies 6 genotypes and >90 subtypes. Genotyaccounts for 70% of HCV-infected persons in the United States and is associated with a poor respotherapy compared with genotypes 2 and 3. The CDC-recommended algorithm for detecting HCV issummarized in Figure 2-1, and the tests to determine the presence of HCV are summarized in TablPatients coinfected with HCV and HIV should be: Advised not to drink excessive amounts of alcohol Evaluated for HCV treatment with interferon plus ribavirin Vaccinated for hepatitis A if susceptibleAvailable data indicate that HCV-HIV co-infection causes more rapid progression of HCV (J Infect D1999;179:1254; Science 1999;285:26.
    • Evaluated for HCV treatment with interferon plus ribavirin Vaccinated for hepatitis A if susceptibleAvailable data indicate that HCV-HIV co-infection causes more rapid progression of HCV (J Infect D1999;179:1254; Science 1999;285:26.Home kit: The FDA has approved a home test kit for HCV. The consumer obtains blood by lancet,blood is placed on a filter strip and submitted by mail to a reading center. Results are available in 10The cost is about $70/test.Figure 2-1: Recommended Testing Algorithim (MMWR 1998;47[RR-20]:27)Table 2-8: Tests for HCVTest Cost CommentAnti-HCV EIA $25 to $45 Includes EIA and RIBA; indicates past or present HCV infection. Sensitivity >97%; EIA lacks specificity in low-prevalence populations - supplemental assay required for confirmation.RIBA $115 to $150HCV RNA $160 to $200 RT-PCR technology to detect HCV RNA; may have false positives and negatives.(HCV RT-PCR)Quantitative $160 to $225 Determines concentration using RT-PCR or bDNA technology; less sensitive than qualitative RT-PCR.HCV PCR Threshold of detection is 500 c/mL; most patients with chronic HCV infection have 10 5 to 107 c/mL. This assay may predict response to therapy but is not useful yet for therapeutic monitoring. It has largely supplanted HCV RNA tests due to increased sensitivity and comparable cost.Genotype $200 to $250 6 genotypes - genotype 1 predominates in the United States (70%) and shows poorest response to therapy. Hepatitis A SerologyThe usual purpose is to identify candidates for HAV vaccine including susceptible persons with chrinfection, injection drug users, gay men, persons with clotting disorders, persons with chronic liver dand travelers to HAV-endemic areas. Some authorities believe that all HIV-infected persons who arsusceptible should be vaccinated for HAV. Susceptibility is defined by negative serologic tests for aThe prevalence of anti-HCV is 62% in injection drug users and 32% in gay men (Clin Infect Dis 199MMWR 1999;48[RR-12]).Top of Page | Next page -- Toxoplasmosis Serology
    • Top of Page | Next page -- Toxoplasmosis SerologyCopyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rights reserved.* Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained in this site because no sor service can take the place of medical training, education, and experience. Consumers are cautioned that this site is not intended to provide medical aspecific medical condition they may have or treatment they may need and they are encouraged to call or see their physician or other health care provideany health related questions they may have.
    • Go to a Chapter Table of Contents Natural History and Classification Tests Disease Prevention Antiretroviral Therapy Management of Opp Infections Drugs: Guide to Information Systems Review HIV in Correc Chapter II: Laboratory Tests Contents: HIV Types and Subtypes Chest X-Ray HIV Serology PPD Skin Testing Alternative HIV Serologic Tests PAP Smears Quantitative Plasma HIV RNA Serology for Hepatitis B Virus (HBV) CD4 Cell Count Testing for Hepatitis C Virus Resistance Testing Toxoplasmosis Serology Screening Battery Cytomegalovirus Serology Complete Blood Count Glucose-6-Phosphate Dehydrogenase Levels Serum Chemistry Panel Adverse Drug Reaction Monitoring Syphilis Serology Tables Table 2-1: Test for HIV-1 Table 2-2: Comparison Between Assay Methods for Viral Load Table 2-3: Comparison of Genotypic and Phenotypic Assays Table 2-4: Letter Designations for Amino Acids Table 2-5: Resistance Mutations Table 2-6: Routine Laboratory Test in Asymptomatic Patients Table 2-7: Recommendations for Intervention Based on Results of PAP Smear Table 2-8: Tests for HCV Toxoplasmosis SerologyToxoplasma serology (IgG) is recommended to assist in the differential diagnosis of complications inthe CNS, to identify candidates for toxoplasmosis prophylaxis if TMP-SMX cannot be taken (since threquires a modified PCP prophylaxis regimen) (Ann Intern Med 1992;117:163), and to counsel patiepreventive measures if seronegative. The preferred method is an agglutination assay for IgG; IgM anot useful, and the Sabin-Feldman dye test is less accurate than the agglutination assay. Toxoplasmseroprevalence among adults in the United States is 10% to 30%, and the seroconversion rate is up1%/year. Most infections in AIDS patients represent relapse of latent infection which is noted in 20%with positive serology and no prophylaxis (Clin Infect Dis 1992;15:211).A negative Toxoplasma serology should be repeated after the CD4 cell count is <100/mm3 if the pacannot take TMP-SMX prophylaxis for PCP or if toxoplasmosis encephalitis is considered when priowere negative. Top of Page | Next page -- Cytomegalovirus SerologyCopyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rights reserved.* Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained in this site because no sor service can take the place of medical training, education, and experience. Consumers are cautioned that this site is not intended to provide medical aspecific medical condition they may have or treatment they may need and they are encouraged to call or see their physician or other health care provideany health related questions they may have.
    • Go to a Chapter Table of Contents Natural History and Classification Tests Disease Prevention Antiretroviral Therapy Management of Opp Infections Drugs: Guide to Information Systems Review HIV in Correc Chapter II: Laboratory Tests Contents: HIV Types and Subtypes Chest X-Ray HIV Serology PPD Skin Testing Alternative HIV Serologic Tests PAP Smears Quantitative Plasma HIV RNA Serology for Hepatitis B Virus (HBV) CD4 Cell Count Testing for Hepatitis C Virus Resistance Testing Toxoplasmosis Serology Screening Battery Cytomegalovirus Serology Complete Blood Count Glucose-6-Phosphate Dehydrogenase Levels Serum Chemistry Panel Adverse Drug Reaction Monitoring Syphilis Serology Tables Table 2-1: Test for HIV-1 Table 2-2: Comparison Between Assay Methods for Viral Load Table 2-3: Comparison of Genotypic and Phenotypic Assays Table 2-4: Letter Designations for Amino Acids Table 2-5: Resistance Mutations Table 2-6: Routine Laboratory Test in Asymptomatic Patients Table 2-7: Recommendations for Intervention Based on Results of PAP Smear Table 2-8: Tests for HCV CMV SerologyThis is advocated by the USPHS/IDSA Guidelines for HIV-infected persons who have low risk for Cinfection, specifically those who are not gay men or injection drug users (MMWR 1999;48[RR-10]:26Possible applications for use of this information are to 1) identify seronegative patients for counselinprevention (although the message is not different from the "safe sex message" for preventing HIVtransmission), 2) assess the likelihood of CMV disease in late-stage HIV infection, and 3) identifyseronegative individuals who should have received CMV-antibody-negative blood or leukocyte-reduproducts for nonemergent transfusions. Seroprevalence for adults in the United States is about 50%men and injection drug users it is >90% (J Infect Dis 1985;152:243; Am J Med 1987;82:593). Top of Page | Next page -- Glucose-6-Phosphate Dehydrogenase LevelsCopyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rights reserved.* Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained in this site because no sor service can take the place of medical training, education, and experience. Consumers are cautioned that this site is not intended to provide medical aspecific medical condition they may have or treatment they may need and they are encouraged to call or see their physician or other health care provideany health related questions they may have.
    • Go to a Chapter Table of Contents Natural History and Classification Tests Disease Prevention Antiretroviral Therapy Management of Opp Infections Drugs: Guide to Information Systems Review HIV in Correc Chapter II: Laboratory Tests Contents: HIV Types and Subtypes Chest X-Ray HIV Serology PPD Skin Testing Alternative HIV Serologic Tests PAP Smears Quantitative Plasma HIV RNA Serology for Hepatitis B Virus (HBV) CD4 Cell Count Testing for Hepatitis C Virus Resistance Testing Toxoplasmosis Serology Screening Battery Cytomegalovirus Serology Complete Blood Count Glucose-6-Phosphate Dehydrogenase Levels Serum Chemistry Panel Adverse Drug Reaction Monitoring Syphilis Serology Tables Table 2-1: Test for HIV-1 Table 2-2: Comparison Between Assay Methods for Viral Load Table 2-3: Comparison of Genotypic and Phenotypic Assays Table 2-4: Letter Designations for Amino Acids Table 2-5: Resistance Mutations Table 2-6: Routine Laboratory Test in Asymptomatic Patients Table 2-7: Recommendations for Intervention Based on Results of PAP Smear Table 2-8: Tests for HCV Glucose-6-Phosphate Dehydrogenase LevelsG6-PD deficiency is a genetic disease that predisposes to hemolytic anemia following exposure to odrugs commonly used in patients with HIV infection. Over 150 G6-PD variants are inherited on the Xchromosome, but the most frequent are Gd A-, which is found in 10% of black men and in 1% to 2%women, and Gd med , found predominantly in men from the Mediterranean area (Italians, Greeks, SepJews, Arabs), India, and Southeast Asia. With most defects, the hemolysis is mild and self-limited bonly the older red cells are involved and the bone marrow can compensate even with continued admof the implicated drug. The important exception is Gd med, which may cause life-threatening hemolysilimited hemolysis in patients with GdA- may be significant in patients with HIV infection, who often haanemia from other causes. The severity of anemia also depends on the concentration of the drug inand the oxidant potential of the inducing agent. The most likely offending agents are dapsone and pSulfonamides cause hemolysis less commonly. G6-PD deficiency may be partial, in which case thecontraindication for oxidant drugs is relative. Options for screening include: 1) obtaining the test at ball patients; 2) restricting testing to those most likely to have a defect; or 3) reserving testing for theoccasional case of hemolytic anemia following exposure to typical inducing agents. Typical findingshemolysis include elevated bilirubin, elevated LDH, decreased haptoglobin, methemoglobinemia,reticulocytosis, and a peripheral smear showing the characteristic "bite cells". During hemolysis, G6are usually normal since the susceptible red cells are destroyed; testing must consequently be delayabout 30 days after discontinuation of the offending agent. Some laboratories report results as unitswith fewer than three indicating severe deficiency, in men and homozygous women; other labs repoqualitative results. Top of Page | Next page -- Adverse Drug Reaction MonitoringCopyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rights reserved.* Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained in this site because no sor service can take the place of medical training, education, and experience. Consumers are cautioned that this site is not intended to provide medical aspecific medical condition they may have or treatment they may need and they are encouraged to call or see their physician or other health care provide
    • Top of Page | Next page -- Adverse Drug Reaction MonitoringCopyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rights reserved.* Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained in this site because no sor service can take the place of medical training, education, and experience. Consumers are cautioned that this site is not intended to provide medical aspecific medical condition they may have or treatment they may need and they are encouraged to call or see their physician or other health care provideany health related questions they may have.
    • Go to a Chapter Table of Contents Natural History and Classification Tests Disease Prevention Antiretroviral Therapy Management of Opp Infections Drugs: Guide to Information Systems Review HIV in Correc Chapter II: Laboratory Tests Contents: HIV Types and Subtypes Chest X-Ray HIV Serology PPD Skin Testing Alternative HIV Serologic Tests PAP Smears Quantitative Plasma HIV RNA Serology for Hepatitis B Virus (HBV) CD4 Cell Count Testing for Hepatitis C Virus Resistance Testing Toxoplasmosis Serology Screening Battery Cytomegalovirus Serology Complete Blood Count Glucose-6-Phosphate Dehydrogenase Levels Serum Chemistry Panel Adverse Drug Reaction Monitoring Syphilis Serology Tables Table 2-1: Test for HIV-1 Table 2-2: Comparison Between Assay Methods for Viral Load Table 2-3: Comparison of Genotypic and Phenotypic Assays Table 2-4: Letter Designations for Amino Acids Table 2-5: Resistance Mutations Table 2-6: Routine Laboratory Test in Asymptomatic Patients Table 2-7: Recommendations for Intervention Based on Results of PAP Smear Table 2-8: Tests for HCV Adverse Drug Reaction MonitoringAdverse drug reactions attributed to antiretroviral agents include diabetes mellitus, blood lipid changassociated with risks for coronary artery disease and stroke, and lactic acidosis/steatosis attributednucleoside analogs (Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and AdoleJanuary 28, 2000, available at http://www.hivatis.org).Diabetes: Risk should be evaluated based on prior diabetes or family history of diabetes, and all pashould be warned of symptoms of hyperglycemia. The median time reported for detecting hyperglycattributed to PIs is at 63 days after initiation of treatment; some authorities recommend fasting bloodmeasurements at 3- to 4- month intervals. Other tests commonly recommended in patients receivinghemoglobin A1C, fasting insulin level, and/or 2-hour glucose tolerance test (GTT) + 2-hour insulin.Blood lipids: Changes include increases in triglycerides and/or cholesterol (total and LDL) with posincreased risk of premature coronary artery disease, cerebrovascular disease, pancreatitis, and choAssessment should include evaluation of risk for cardiovascular disease, including family history, mehistory, smoking history, weight, blood pressure, diabetes, baseline levels, and magnitude of lipid chThe mean increase in cholesterol with PI-containing HAART regimens is 32 mg/dL at 3.4 months anmean LDL increase is 18 mg/dL. Recommendations from the ACTG for monitoring are fasting triglyctotal cholesterol and HDL cholesterol; LDL is the single most important measurement for cardiovascassessment and requires a fasting triglyceride measurement of <400 mg/dL for accurate measuremInfect Dis 2000;31:1216). Fasting should be done for at least 8 hours and preferably 12 hours. Therecommendation is for risk assessment and baseline studies with subsequent tests at 3 to 6 monthsrepeat according to these results and risk assessment. Intervention is based on the National CholesEducation Program Treatment (Circulation 1994;89:1329) (see Table 4-24).Lactic acidosis and hepatic steatosis: Routine therapeutic monitoring is not recommended, but laacidosis should be considered in patients who are receiving nucleoside analogs who have unexplainsymptoms of lactic acidosis, including fatigue, abdominal pain, vomiting, hepatitis, and weight loss. Tconsider include assessment of lactic acid levels, LDH, ALT, and CPK. Venous lactic acid levels >2
    • Education Program Treatment (Circulation 1994;89:1329) (see Table 4-24).Lactic acidosis and hepatic steatosis: Routine therapeutic monitoring is not recommended, but laacidosis should be considered in patients who are receiving nucleoside analogs who have unexplainsymptoms of lactic acidosis, including fatigue, abdominal pain, vomiting, hepatitis, and weight loss. Tconsider include assessment of lactic acid levels, LDH, ALT, and CPK. Venous lactic acid levels >2are abnormal; patients with levels of 2 to 5 mmol/L may have modest symptoms or be asymptomaticwith levels of 5 to10 mmol/L are usually symptomatic; and levels >10 mmol/L are always associatedsymptoms and are often fatal (8th Conference on Retroviruses and Opportunistic Infections (CROI),Ill., February 2001, Abstract 540). Top of Page | Next page -- Chapter III: Disease PreventionCopyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rights reserved.* Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained in this site because no sor service can take the place of medical training, education, and experience. Consumers are cautioned that this site is not intended to provide medical aspecific medical condition they may have or treatment they may need and they are encouraged to call or see their physician or other health care provideany health related questions they may have.
    • Go to a Chapter Table of Contents Natural History and Classification Tests Disease Prevention Antiretroviral Therapy Management of Opp Infections Drugs: Guide to Information Systems Review HIV in Correc III. Disease Prevention: Prophylactic Antimicrobial Agents and Vaccines Recommendations of the USPHS/IDSA Guidelines for the Prevention of Opportunistic Infections in Infected with Human Immunodeficiency Virus: (http://www.hivatis.org; MMWR 1999;48[RR-10]; Cl Dis 2000;30:Supplement 1) Strongly Recommended as Standard of Care Generally Recommended Not Recommended for Most Patients Tables Table 3-1: Categories Reflecting Strength and Quality of EvidenceTable 3-1: Categories Reflecting Strength and Quality of EvidenceRating System for Strength of Recommendation and Quality of Evidence Supporting the RecommendationCategory Definition Categories Reflecting the Strength of Each Recommendation A Both strong evidence for efficacy and substantial clinical benefit support recommendation for use. Should always be offered. B Moderate evidence for efficacy - or strong evidence for efficacy, but only limited clinical benefit - supports recommendation for use. Should be offered. C Evidence for efficacy is insufficient to support a recommendation for or against use, or evidence for efficacy may not outweigh adverse consequences (eg, toxicity, drug interactions, or cost of the chemoprophylaxis or alternative approaches). Optional. D Moderate evidence for lack of efficacy or for adverse outcome supports a recommendation against use. Should generally not be offered. E Good evidence for lack of efficacy or for adverse outcome supports a recommendation against use. Should never be offered. Categories Reflecting Quality of Evidence Supporting the Recommendation I Evidence from at least one properly randomized, controlled trial. II Evidence from at least one well-designed clinical trial without randomization, from cohort or case-controlled analytic studies (preferably from than one center), or from multiple time-series studies or dramatic results from uncontrolled experiments. III Evidence from opinions of respected authorities based on clinical experience, descriptive studies, or reports of expert committees. Strongly Recommended as Standard of CarePneumocystis carinii
    • Risk: CD4 cell count <200/mm3, prior PCP or HIV-associated thrush or unexplained fever x 2weeks. (AII)*Preferred: TMP-SMX 1 DS/day or 1 SS/day (AI)Alternatives: TMP-SMX 1 DS 3x/week (BI) Dapsone 100 mg/day or 50 mg PO bid (BI) Dapsone 50 mg/day plus pyrimethamine 50 mg/week plus leucovorin 25 mg/week (BI) Dapsone 200 mg/week plus pyrimethamine 75 mg/week plus leucovorin 25 mg/week (BI) Aerosolized pentamidine 300 mg/month by Respirgard II nebulizer using 6 mL diluent delivered at 6 L/min from a 50 psi compressed air source until reservoir is dry (usually 45 minutes) with or without albuterol (2 whiffs) to reduce cough and bronchospasm (BI) Atovaquone 1500 mg PO qd with meals (N Engl J Med 1998;339:1889) (BI)Comments: The risk of PCP without prophylaxis is 60% to 70% per year in those with priorPCP and 40% to 50%/year for those with a CD4 cell count <100/mm3. The mortality forpatients hospitalized with PCP is 15% to 20%. PCP prophylaxis reduces the risk of PCP9-fold, and patients who get PCP despite prophylaxis have a low mortality rate (Am J RespirCrit Care Med 1997;155:60). The major reasons for PCP prophylaxis failure are CD4 cell coun<50/mm 3 and non-compliance (JAMA 1995;273:1197; Arch Intern Med 1996;156:177).TMP-SMX has established efficacy for reducing the incidence of bacterial infections andtoxoplasmosis. This drug is active against Nocardia, legionella, most Salmonella, mostmethicillin-sensitive S. aureus, many gram-negative bacilli, most H. influenzae, and about 70%of S. pneumoniae. No other PCP prophylaxis regimen has this spectrum of activity. Adversereactions sufficiently severe to require discontinuation of the drug are noted in 25% to 50%with TMP-SMX, 25% to 40% with dapsone, and 2% to 4% with aerosolized pentamidine (NEngl J Med 1995:332:693). Patients who have a non-life-threatening reaction to TMP-SMXshould continue this drug if it can be tolerated. Those who have had such a reaction in thepast should be rechallenged, possibly using desensitization. Gradual initiation of TMP-SMXprophylaxis reduces the rate of rash and/or fever by about 50% (J AIDS 2000;24:337) (seeregimen). This suggests that most reactions are not allergic or IgE mediated. Patients givendapsone should be tested for G6-PD deficiency if at risk. Data are inadequate to establish theefficacy and safety of parenteral pentamidine (4 mg/kg/month), or clindamycin-primaquine.Fansidar is rarely used due to possible severe hypersensitivity reactions.Immune reconstitution: Patients who have increases in CD4 cell count to >200/mm3 x >3months may safely discontinue primary PCP prophylaxis (CII) (N Engl J Med 1999;340:1301;Lancet 1999;353:1293; Lancet 1999;353:201; J Infect Dis 2000;181:1635). Data are nowadequate to make this recommendation for secondary PCP prophylaxis as well. Two studieswith a total of 438 patients with prior PCP stopped prophylaxis when the CD4 cell countexceeded 200 cells/mm3. There were no cases of P. carinii pneumonia with mean follow-upperiods of 13 and 20 months (N Engl J Med 2001:344:159; N Engl J Med 2001;344:168). Itshould be noted that although the protocol criterion to discontinue prophylaxis was a CD4 cellcount of 200 cells/mm3, the mean CD4 cell count at the time of discontinuation was 350cells/mm3 in both studies.
    • with a total of 438 patients with prior PCP stopped prophylaxis when the CD4 cell count exceeded 200 cells/mm3. There were no cases of P. carinii pneumonia with mean follow-up periods of 13 and 20 months (N Engl J Med 2001:344:159; N Engl J Med 2001;344:168). It should be noted that although the protocol criterion to discontinue prophylaxis was a CD4 cell count of 200 cells/mm3, the mean CD4 cell count at the time of discontinuation was 350 cells/mm3 in both studies. Recommendation for primary and secondary prophylaxis: Discontinue prophylaxis when CD4 cell count is >200 x>3 months (AI). Restart prophylaxis when CD4 cell count is <200/mm (AIII). Contact: Some authorities recommend avoidance of "high-intensity exposure," meaning that a patient with PCP should not room with a vulnerable patient (N Engl J Med 2000;342:1416; Am J Respir Crit Care 2000;162:167).M. tuberculosis Risk: (MMWR 1998;47[RR-20]): Positive PPD (>5mm induration) without prior prophylaxis or treatment (AI), recent TB contact (AII), or history of inadequately treated TB that healed (AII) (MMWR 2000;49[RR-6]). Preferred (MMWR 2000;49[RR-6]; MMWR 2001;50:773): INH 300 mg + pyridoxine 50 mg PO qd x 9 months (AII); or INH 900 mg + pyridoxine 100 mg PO 2x/week x 9 months (BII). Alternative without concurrent PI or NNRTI: RIF 600 mg PO qd x 4 months (BIII) or PZA 15-20 mg/kg qd x 2 months + RIF 600 mg qd (BI) (see monitoring advocated for the PZA + RIF/RFB regimens - next page). Alternative with concurrent PI or NNRTI: Rifabutin (RBT) in place of RIF (CIII) with the following dose regimens for RFB and the concurrent PI or NNRTI. APV - 1200 mg bid; RBT - 150 mg/day or 300 mg 2x/week EFV - standard; RBT - 450 mg/day or 600 mg 2x/week IDV - 1000 mg q8h; RBT - 150 mg/day or 300 mg 2x/week NFV - 1000 mg tid or 1250 mg bid; RBT - 150 mg/day or 300 mg 2x/week RTV - standard dose; RBT - 150 mg qod LPV/RTV - standard dose; RBT -150 mg qod NVP - 200 mg bid; RBT 300 mg/day Note: RFB should not be combined with RTV or DLV and dose schedules are not available for Fortovase (FTV). RIF or RFB should be combined with pyrazinamide 20 mg/kg/day with >60 doses x 2 months or up to 3 months with interruptions (BIII). RIF 600 mg qd x 4 months (BII) Contact with INH resistant strain: RIF plus pyrazinamide x 2 months (above doses) (AI) Alternative: RIF/PZA (above doses x 2 months) (BIII); RBT 300 mg/day PO x 4 months (CIII). Contact with strain resistant to INH and rifamycin: Use 2 agents with anticipated activity - ethambutol (EMB)/pyrazinamide or levofloxacin/pyrazinamide Pregnancy: INH regimens
    • Contact with strain resistant to INH and rifamycin: Use 2 agents with anticipated activity - ethambutol (EMB)/pyrazinamide or levofloxacin/pyrazinamide Pregnancy: INH regimens Monitoring: Recipients of PZA + RIF/RFB: Hepatotoxicity with 6 deaths have been reported with the PZA + RIF 2 month regimen (MMWR 2001;50:733). This regimen is preferred for HIV-infected patients who are considered unlikely to complete the 9 month INH regimen. Monitoring should include patient visits at 0, 2, 4, 6, and 8 weeks with bilirubin + ALT measurements at 0, 2, 4, and 6 weeks. Discontinue prophylaxis with ALT elevations to 5x ULN in asymptomatic patients and any elevation of ALT when accompanied by hepatitis symptoms Recipients of INH: Clinical monitoring at monthly intervals. Bilirubin ALT, AST, and CBC measurements at baseline, 3 months, and p.r.n. Patient should report any symptoms of hepatitis - jaundice, dark urine, nausea, vomiting, abdominal pain, and/or fever >3 days. INH should be discontinued with ALT elevation to >5x ULN without symptoms or ALT >3x ULN wit symptoms.Toxoplasma gondii Risk: CD4 cell count <100/mm3 plus positive IgG serology for T. gondii. Preferred: TMP-SMX 1 DS/day (AII) Alternatives: TMP-SMX 1 SS/day (BIII) Dapsone 50 mg/day PO plus pyrimethamine 50 mg/week plus leucovorin 25 mg/week (BI) Dapsone 200 mg PO/week plus pyrimethamine 75 mg PO/week plus leucovorin 25 mg PO/week Atovaquone 1500 mg/day + pyrimethamine 25 mg/day + leucovorin 10 mg/day (CIII). Immune reconstitution: Studies now confirm the safety of discontinuing primary prophylaxis for toxoplasmosis when the CD4 cell count is >200/mm3 for >3 months. This is supported by trials in 554 patients representing 400 patient-years with no cases (Lancet 2000;355: 2217; J Infect Dis 2000;181:1635). It also appears safe to discontinue maintenance therapy for toxoplasmosis when the CD4 cell count is >200/mm 3 for 6 to 12 months (AIDS 1999;13:1647; AIDS 2000;14:383; 13th Intl. AIDS Conf., Durban, South Africa, July 2000, Abstract 2283). Recommendation: Primary prophylaxis: Discontinue prophylaxis with CD4 cell count >200/mm3 for >3 months (AI); restart when CD4 cell count is <100-200/mm 3 (AIII). Secondary prophylaxis: Discontinue prophylaxis >6 months, completed initial therapy, and asymptomatic for toxoplasmosis (CIII); restart prophylaxis when CD4 cell count is <200/mm3 (AIII).M. avium complex
    • Risk: CD4 cell count <50 mm3*. Note: Physician compliance with this recommendation is only about 50%, compared with 80% for PCP (N Engl J Med 2000;342:1416). Preferred: Clarithromycin 500 mg or PO bid (AI) or azithromycin 1200 mg PO weekly (AI). Alternative: RBT 300 mg/day PO (BI) or azithromycin 1200 mg/week plus RBT 300 mg/day (CI) (see rifabutin dose adjustment for use with PIs or NNRTIs). Use caution when RBT is combined with clarithromycin due to drug interactions (J Infect Dis 2000;181:1289). Immune Reconstitution: It appears safe to discontinue primary MAC prophylaxis when the CD4 cell count has increased to >100/mm3 for 3 months (CII) (N Engl J Med 1998;338:853; N Engl J Med 2000;342:1085; Ann Intern Med 2000;133:493). One study showed that 2 of 321 patients subsequently developed focal infections of the vertebral spine several months after stopping azithromycin. It also appears safe to discontinue maintenance therapy for MAC when the CD4 cell count is >100/mm3 x 6 to 12 months (J Infect Dis 1998;178:1446; 40th ICAAC, Toronto, Canada, September 2000, Abstract 1912). Recommendation: Primary prophylaxis: Discontinue prophylaxis with CD4 cell count >100/mm3 for >3 months (AI); restart when CD4 cell count is <50-100/mm3 (AIII). Secondary prophylaxis: Discontinue prophylaxis when CD4 cell count is >100/mm3 for >6 months, completed 12 month therapy, and asymptomatic for MAC (CIII); restart when CD4 ce count is <100/mm 3 (AIII).Varicella Risk (primary infection): Significant exposure to chickenpox or shingles in individuals who are either seronegative for VZV or have no history of primary or secondary VZV. Preferred: VZIG 5 vials (6.25 mL) IM within 96 hours of exposure, preferably within 48 hours (AIII). Alternative: Prophylactic acyclovir was included in the 1995 USHS/IDSA Guidelines but was deleted from the 1999 version due to lack of supporting clinical evidence of efficacy.
    • Top of Page | Next page -- Generally RecommendedCopyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rights reserved.* Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained in this site because no sreference or service can take the place of medical training, education, and experience. Consumers are cautioned that this site is not intended to provideadvice about any specific medical condition they may have or treatment they may need and they are encouraged to call or see their physician or other hprovider promptly with any health related questions they may have.
    • Go to a Chapter Table of Contents Natural History and Classification Tests Disease Prevention Antiretroviral Therapy Management of Opp Infections Drugs: Guide to Information Systems Review HIV in Correc III. Disease Prevention: Prophylactic Antimicrobial Agents and Vaccines Recommendations of the USPHS/IDSA Guidelines for the Prevention of Opportunistic Infections in Infected with Human Immunodeficiency Virus: (http://www.hivatis.org; MMWR 1999;48[RR-10]; Cl Dis 2000;30:Supplement 1) Strongly Recommended as Standard of Care Generally Recommended Not Recommended for Most Patients Tables Table 3-1: Categories Reflecting Strength and Quality of Evidence Generally RecommendedS. pneumoniae Risk: All patients with HIV infection. Risk for invasive pneumococcal infection is 50- to 100-fold greater than in the general population (Ann Intern Med 2000;132:182; J Infect Dis 1996;173:857). Preferred: Pneumovax 0.5 mL IM x 1 (CD4 cell count >200/mm3 - BII; CD4 cell count <200/mm3 - CIII). Revaccinate: When CD4 cell count increases to >200/mm3 if initial immunization was given with CD4 cell count <200/mm 3 (CIII) (MMWR 1999[RR-10]:16). A subsequent report by leader of the OI guideline panel recommended re-vaccination at 3 to 5 year intervals (N Engl J Med 2000;342:1416), but see "Note" below. Alternative: The 7 valent protein-conjugated pneumococcal vaccine approved by the FDA in March 2000 is recommended only for children, but studies in adults are ongoing since this may be a superior immunogen in immunosuppressed patients. Note: Studies of pneumococcal vaccine in HIV-infected persons have shown variable results. A CDC report indicated 49% efficacy (Arch Intern Med 2000;160:2633). Others show poor efficacy in immunosuppressed hosts (N Engl J Med 1986;315:1318; JAMA 1993;270:1826), and a study in Uganda showed increased rates of pneumococcal disease in vaccine recipients (Lancet 2000;355:2106). Some authorities think this result may be idiosyncratic to the location of the study. Based on the controversial data regarding efficacy, the OI Guidelines Panel has deleted Pneumovax as a recommended performance indicator (Clin Infect Dis 2000;30:51).Hepatitis B
    • Risk: Negative anti-HBc or anti-HBs screening test Preferred: Recombivax HB 10 µg IM x 3 (BII) or Enerix-B 20 µg IM x 3 (BII).Influenza Risk: All patients annually. Preferred: Influenza vaccine 0.5 mL IM each year, preferrably October - November (BIII). Alternative: Amantadine 100 mg PO bid (CIII) or rimantadine 100 mg PO bid (CIII). (Note: Zanamivir [Relenza, 10 mg inhaled/day] or osteltamivir [Tamiflu, 75 mg/day] are also active fo prophylaxis and are active against both influenza A & B. Oseltamivir, rimantadine, and amantadine are FDA-approved for prophylaxis).Hepatitis A Risk: Susceptible patients with chronic hepatitis C infection (can be considered in all susceptible patients). Preferred: Havrix 0.5 mL IM x 2 separated by 6 months (BIII). Top of Page | Next page -- Not Recommended for Most PatientsCopyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rights reserved.* Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained in this site because no sreference or service can take the place of medical training, education, and experience. Consumers are cautioned that this site is not intended to provideadvice about any specific medical condition they may have or treatment they may need and they are encouraged to call or see their physician or other hprovider promptly with any health related questions they may have.
    • Go to a Chapter Table of Contents Natural History and Classification Tests Disease Prevention Antiretroviral Therapy Management of Opp Infections Drugs: Guide to Information Systems Review HIV in Correc III. Disease Prevention: Prophylactic Antimicrobial Agents and VaccinesRecommendations of the USPHS/IDSA Guidelines for the Prevention of Opportunistic Infections inInfected with Human Immunodeficiency Virus: (http://www.hivatis.org; MMWR 1999;48[RR-10]; ClDis 2000;30:Supplement 1) Strongly Recommended as Standard of Care Generally Recommended Not Recommended for Most PatientsTables Table 3-1: Categories Reflecting Strength and Quality of Evidence Not Recommended for Most Patients; Consider for Selected PatientsCryptococcosis Risk: CD4 cell count <50/mm3. (Can be considered in all susceptible patients). Preferred: Fluconazole 100-200 mg/day PO (CI). Alternative: Itraconazole 200 mg/day PO (CIII). Immune reconstitution: Discontinue secondary prophylaxis when CD4 cell count is >100-200/mm3 for >6 months, initial therapy completed, and asymptomatic for cryptococcosis (CIII); restart secondary prophylaxis when CD4 cell count is <100-200/mm3 (AIII).Histoplasmosis Risk: CD4 cell count <100/mm3 plus residence in endemic area. Preferred: Itraconazole 200 mg/day PO (CI). Immune reconstitution: No criteria for discontinuing secondary prophylaxis.Coccidioidomycosis
    • Risk: CD4 cell count <200/mm3 (J Infect Dis 2000;181:1428). The frequency in the endemic area is about 4% per year in AIDS patients, 0.2% per year for HIV without AIDS, and 0.015% per year in the general population (J Infect Dis 2000;181:1428). Preferred: Fluconazole 400 mg/day PO or itraconazole 200 mg bid PO (secondary prophylaxis) Immune reconstitution: No criteria for discontinuing secondary prophylaxis.CMV Risk: CD4 cell count <50/mm3 plus positive CMV serology. Preferred: Oral ganciclovir 1 g PO tid (CI). Maintenance therapy: Consider discontinuation of therapy when the CD4 cell count >100 to 150/mm3 for >3 to 6 months. This decision should be made with a concurring ophthalmologist based on duration and magnitude of the CD4 response, location of the retinal lesion, vision in the contralateral eye, and availability of ophthalmologic follow-up. The initial experience with discontinuation has been favorable (J Infect Dis 1998;177:1182; J Infect Dis 1998;177:1080; Opthalmology 1998;105:1259; JAMA 1999;282:1633; AIDS 1999;13:647). Nevertheless, there are isolated cases of relapses even with CD4 cell counts >400/mm3 (N Engl J Med 2000;342:1416). Immune reconstitution: Secondary prophylaxis can be discontinued when the CD4 cell coun is >100-150/mm3, there is no evidence of active disease and there will be regular ophthalmic exams (BII); restart secondary prophylaxis when the CD4 cell count is <100-150/mm3 (AIII).Bacterial infection Risk: Neutropenia. Preferred: G-CSF 5-10 µg/kg/day SC x 2 to 4 weeks or GM-CSF 250 µg/m2/day-IV over 2 hours x 2 to 4 weeks (CII). (Authors comment: The recommendation given is from the CDC guidelines; the authors think this dose is somewhat unrealistic and wasteful. Most start with a 300 mg vial qd or qod and titrate down).
    • Top of Page | Next page -- Chapter IV: Antiretroviral TherapyCopyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rights reserved.* Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained in this site because no sreference or service can take the place of medical training, education, and experience. Consumers are cautioned that this site is not intended to provideadvice about any specific medical condition they may have or treatment they may need and they are encouraged to call or see their physician or other hprovider promptly with any health related questions they may have.
    • Go to a Chapter Table of Contents Natural History and Classification Tests Disease Prevention Antiretroviral Therapy Management of Opp Infections Drugs: Guide to Information Systems Review HIV in CorrecIV. Antiretroviral Therapy Recommendations for Antiretroviral Therapy Goals of Therapy Terms and Concepts Antiretroviral Therapy for HIV Infected Patients Recommendations for Antiretroviral Therapy in Pregnancy Postexposure Prophylaxis for Health Care Workers Postexposure Prophylaxis for Sexual Contact or Needle Sharing Antiretroviral Agents Nucleoside Analogs Non-nucleoside Reverse Transcriptase Inhibitors (NNRTI) Protease Inhibitors Class Adverse Reactions to Antiretroviral Agents Tables Table 4-16: Antiretroviral Drugs Approved by FDA for HIV Table 4-20: Drugs That Should Not be Used with Protease Inhibitors or NNRTIs* Table 4-21: Drug Interactions Requiring Dose Modifications or Cautious Use Table 4-22: Drug Interactions: Protease Inhibitors and Non-Nucleoside Reverse Transcriptase Inhibitors Effect of Drug on Levels(AUCs)/Dose Table 4-27: HIV-Related Drugs with Overlapping Toxicities Table 4-28: Dosing of Antiretroviral Agents in Renal and Hepatic Failure Table 4-29: Characteristics of Antiretrovirals During Dialysis I. Recommendations for Antiretroviral TherapyBased on the recommendations of the DHHS/Kaiser Family Foundation as of May 2001;(DHHS Panel on Clinical Practices for Treatment of HIV Infection Guidelines for Use ofAntiretroviral Agents in HIV-infected Adults and Adolescents); available athttp://www.hivatis.org. Print copies may be obtained from HIV/AIDS Treatment InformationService, P.O. Box 6303, Rockville, MD 20849-6303; telephone: 800-448-0440.
    • GOALS OF THERAPY Clinical goals: Prolongation of life and improved quality of life Virologic goals: Greatest possible reduction in viral load (preferably to <20 c/mL) for as long as possible to: 1) halt disease progression, and 2) prevent/reduce resistant variants. Note that CD4 response is often good with partial viral suppression, and opportunistic infections (OIs) are uncommon with a viral load <5000 c/mL (J Infect Dis 2000;181:946). However, partially suppressive regimens are less durable and lead to the emergence of drug-resistant virus. Immunologic goals: Immune reconstitution that is quantitative (CD4 cell count in normal range) and qualitative (pathogen-specific immune response). Therapeutic goals: Rational sequencing of drugs in a fashion that achieves virologic goals, but also: 1) maintains therapeutic options; 2) is relatively free of side effects; and 3) is realistic with regard to probability of adherence Epidemiologic goals: Reduce HIV transmissionTERMS AND CONCEPTS Blips: Transient detectable viremia after a period of no detectable virus. It is usually defined as a viral load of 50 to 500 c/mL after viral load <50 c/mL on at least two consecutive occasions. There are three possible outcomes following an increase in viral load to detectable levels: return to undetectable (only this is a blip), sustained low-level viremia (viral load 50 to 500 c/mL), or virologic failure (>500 c/mL). Blips are seen in 40% to 50% of patients who achieve levels <50 c/mL; these patients usually have higher baseline HIV RNA levels when using more sensitive quantitative assays. Patients who experience recurrent blips have a modestly increased risk of eventual virologic failure (8th CROI, Chicago, Ill., February 2001, Abstract 522). Class-sparing regimens: Regimens that avoid exposure to drug classes, allowing the preservation of these agents for subsequent therapy. NNRTI/NRTI combinations are often referred to as "PI-sparing." NRTI-based regimens, such as AZT/3TC/ABC, spare both PIs and NNRTIs for future use. Cure: It is unfortunate that the cure theory was deemed plausible, since it had an enormous impact on patient perceptions of the benefits of therapy. All studies show persistent viral infection even when there are prolonged periods of undetectable virus with the ultra-sensitive quantitative HIV RNA assays (N Engl J Med 1999;340:1605; Nat Med 1999;5:512). Discordance - CD4 cell count/viral load: A paradoxical increase in CD4 cell count despite poor virologic control or a failure of a significant CD4 response despite good virologic control. Analysis of data on 2236 French patients given initial HAART showed that 48% had a good virologic and immunologic response (viral load <1000 c/mL and CD4 increase >50 cells/mm 3 at 6 months), 16% had no
    • Discordance - CD4 cell count/viral load: A paradoxical increase in CD4 cellcount despite poor virologic control or a failure of a significant CD4 responsedespite good virologic control. Analysis of data on 2236 French patients giveninitial HAART showed that 48% had a good virologic and immunologic response(viral load <1000 c/mL and CD4 increase >50 cells/mm 3 at 6 months), 16% had noresponse, 19% had only a CD4 response, and 17% had only a virologic response(Ann Intern Med 2000;133:401). These data suggest discordance in 36%,although the frequency is completely dependent on definitions. Most reportparadoxical increases in CD4 response with failure to control viral load. Forexample, analysis of the Swiss Cohort study (Lancet 1999;353;863) showed thatpatients with persistent viral suppression had an average CD4 cell count increaseof 138/mm 3, compared with an increase of 130/mm3 in those with only a transientvirologic response (Lancet 1998;351:723; AIDS 1999;13:2547). Similarconclusions result from analyses of OIs. Thirty-month follow-up data from 2674patients treated with PI combination regimens showed that the frequency of OIswas 6.6% for those with viral control, 20.1% for nonresponders, and about 55% forhistoric controls (Lancet 1999;353:863). These studies demonstrate that patientsfailing HAART often have CD4 responses to therapy and reduced clinicalprogression. In many cases there is also partial viral suppression, so that thediscordance may be relative (J Infect Dis 2000;181:946). An analysis of 380patients with a 96-week follow-up showed the CD4 response was less durablewhen the viral load response was transient or partial (J Infect Dis 2000;181:946).However, benefit may be observed even when viral load returns to baseline,presumably due to reduced "fitness" of HIV. The durability of this benefit isunknown beyond the 1 to 2 years observed in the studies summarized above.GART: Genotypic antiretroviral resistance testingGenetic barrier to resistance: The mutations required by antiretroviral agents forevolution of phenotypic or clinically significant resistance. Examples of drugs withlarge genetic barriers include PIs other than NFV and all NRTIs except 3TC.HAART (highly active antiretroviral therapy): An antiretroviral regimen that canreasonably be expected to reduce the viral load to <50 c/mL in treatment-naïvepatients.Immune-based therapy: Treatment intended to achieve immune reconstitutionthat does not involve antiretroviral therapy. The most advanced forms ofimmune-based therapy in development through clinical trials are interleukin (IL)-2and gp120 depleted inactivated HIV vaccine (Remune). Trials of IL-2 therapyshow robust CD4 responses using doses of 5.0 to 7.5 million international units(MIU) twice daily intramuscularly (IM) or subcutaneously (SC) x 5 days every 8weeks; most studies have been carried out in patients with baseline CD4 cellcounts >200/mm3 (Lancet 1999;535:1923). More recent studies show a modestresponse in patients with more advanced disease as well (J Infect Dis1999;180:56). Remune and other therapeutic vaccines are given to stimulateHIV-specific CTL response for improved immune regulation of HIV; preliminaryresults document immune response, but have not confirmed clinical benefit inrates of clinical progression, death, viral load levels, body weight, or CD4percentage (JAMA 2000;284:2193). Similarly disappointing preliminary resultswere obtained with a recombinant gp160 vaccine (Lancet 1999;353:1735).Immune reconstitution: The immune response to antiretroviral therapy isquantitative (CD4 response) and qualitative (antigen/microbe specific). The initialresponse is an increase in CD38 + MO + (memory) cells, which is followed after 6months by increases in CD38+ MA+ (naïve) cells including naïve cells of thymic
    • Immune reconstitution: The immune response to antiretroviral therapy isquantitative (CD4 response) and qualitative (antigen/microbe specific). The initialresponse is an increase in CD38 + MO + (memory) cells, which is followed after 6months by increases in CD38+ MA+ (naïve) cells including naïve cells of thymicorigin. The biologic impact of immune reconstitution has been demonstrated by 1)an inflammatory response ascribed to immunologic reaction to selected microbialantigens (see "Immune Reconstitution Syndrome" below), 2) the safety ofdiscontinuing of prophylaxis for selected OIs; 3) control of several chronic,untreatable opportunistic infections as a result of HAART; and 4) an impressivedecline in virtually all HIV-associated complications except lymphomas. Chronic,relatively untreatable infections that can be controlled with immune reconstitutioninclude Molluscum contagiosum, PML, CMV, cryptosporidiosis, andmicrosporidiosis. OI prophylaxis that may be suspended with adequate criteria forimmune reconstitution includes primary and secondary prophylaxis for virtually allOIs (MMWR 1999;48[RR-10]; N Engl J Med 2001;344:159; J Infect Dis2000;181:1635; N Engl J Med 2001;344:168; Ann Intern Med 2000;133:493;Lancet 2000;335:2217).Immune reconstitution syndrome: This refers to a group of conditions that recurafter prior quiescence, apparently due to immune restoration resulting fromHAART. The syndrome includes focal MAC, cryptococcal meningitis with amarked CSF pleocytosis, mild herpes zoster, PML with contrast enhancement,CMV vitritis, and progression of TB lesions with sparse organisms. Thepathogenesis is unclear, but some speculate that it reflects restoration of CD4 orCD8 competency, or that it may be cytokine-mediated (Ann Intern Med2000;133:447). Recommendations for management vary by pathogen and clinicalexpression, but most involved drugs directed against the pathogen with or withoutanti-inflammatory agents. Commom examples include:Table 4-1: Immune Reconstitution SyndromesOI Clinical Features TreatmentMAC Focal adenitis, granulomatous masses MAC therapy, steroidsCMV Vitritis CMV therapy, local steroidsTB Pneumonitis, lymphadenitis, TB treatment & anti-infammatory sparse acid-fast bacillus (AFB) agents + steroidsCryptococcosis Meningitis with high CSF WBC Antifungal therapyHCV Active hepatitis, cirrhosis, Interferon + ribavirin cryoglobulinemiaHerpes zoster Mild disease Anti-varicella zoster virus (VZV) therapyPML Neurologic deficits, MRI with peripheral Continue HAART enhancementIntensification: The addition of antiretroviral agents to an existing regimen,usually due to failure to achieve a desired virologic response despite evidence ofreduced viral load. This may be considered in early treatment (viral load >500c/mL at 8 to 16 weeks), if optimal viral suppression has not been achieved (>20c/mL at >24 to 36 weeks), or at the time of viral rebound. International AIDSSociety USA (IAS-USA) Guidelines (JAMA 2000;283:381) recommendconsideration of intensification at 8 to 16 weeks if goals for viral load are notachieved.
    • reduced viral load. This may be considered in early treatment (viral load >500c/mL at 8 to 16 weeks), if optimal viral suppression has not been achieved (>20c/mL at >24 to 36 weeks), or at the time of viral rebound. International AIDSSociety USA (IAS-USA) Guidelines (JAMA 2000;283:381) recommendconsideration of intensification at 8 to 16 weeks if goals for viral load are notachieved.Multi-drug rescue therapy ("mega-HAART"): Salvage or rescue regimenscontaining >6 antiretroviral regimens. Some of the drugs are "recycled." Therationale is that patients with multiple drug exposure and failures are unlikely to beinfected with virus that is resistant to all drugs. Preliminary data from trials inpatients with multi-drug resistant strains demonstrate some success with thisapproach; the main concerns are cost, toxicity, side effects, drug interactions, andthe need for extraordinary motivation.Pharmacologic barrier to resistance: The achievement of tissue levels ofpharmacologically active drugs substantially above the IC 50 or IC90 for prolongedperiods. Examples of drugs with large pharmacologic barriers include EFV, NVP,and lopinavir/ritonavir (LPV/RTV).Replicative (viral) fitness: The concept that certain mutations, includingmutations that confer resistance, may decrease the replicative capacity of HIV.This can be measured by comparative growth kinetics of strains with and withoutselected mutations or with a competitive assay (J Virol 1999;73:3744). An exampleis the RT 184 mutation, which confers 3TC resistance but also reduces HIV fitnessfor replication. Data from in vitro studies demonstrate that protease mutations atcodons 30 and 90 reduce in vitro replicative capacity, whereas multiply mutatedstrains resistant to IDV showed no difference compared to wild type virus,presumably because they also contain compensatory mutations that improvefitness (J Virol 999;73:3744).Resistance testing: Genotypic resistance testing measures mutations on thereverse transcriptase and/or protease gene that impart partial or completeresistance to HIV. Results are interpreted on the basis of established patterns ofmutations associated with phenotypic resistance, but assess only the predominantstrain(s), require expertise for interpretation, and usually do not detect resistanceto discontinued agents due to substitution by wild type strains. Phenotypicresistance testing provides the ratio of the IC50 (concentration necessary to inhibit50% of strains) of the patients virus compared with wild type virus, to give "folddecrease in susceptability." This test is more easily interpreted by care providers,but is expensive (~$600 to $900/test); results are not available for >2 weeks; onlythe dominant strains are tested, and thresholds that define resistance arearbitrary, and may not correlate with in vivo resistance or achievable serumconcentrations. Despite the limitations, multiple studies show that resistancetesting usually improves drug selection in "rescue regimens." These studiesinclude VIRADAPT (Lancet 1999;353:2191), CPCRA 046 (6th CROI, Chicago, Ill.,February 1999, Abstract LB8), ACTG 372, the Stanford study (Ann Intern Med1999;131:813), VIRA 3001 (7th CROI, San Francisco, Calif., February 2000,Abstract 237), and the HAVANNA study (8th CROI, Chicago, Ill., February 2001,Abstract 434). Nearly all of these reports show that adherence and expertise indecision making are the critical variables for successful outcomes.Salvage therapy: Treatment regimens used in patients who have failed at leasttwo antiretroviral regimens and have had extensive exposure to antiretroviralagents. Some prefer the term "rescue therapy," and some use these terms for anypatient who has failed HAART.
    • Salvage therapy: Treatment regimens used in patients who have failed at leasttwo antiretroviral regimens and have had extensive exposure to antiretroviralagents. Some prefer the term "rescue therapy," and some use these terms for anypatient who has failed HAART.Second-generation antiretrovirals: Drugs currently in development that areactive against HIV strains resistant to current members of those classes.Structured treatment interruption (STI): STI is the planned interruption oftreatment by discontinuation of all antiretroviral drugs. There are four reasons toconsider STI:1. One reason the "drug holiday," in which the purpose is to relieve the patient ofthe inconvenience and toxicity of unsuccessful antiretroviral therapy and toimprove response to salvage therapy by allowing re-emergence of wild type virus.The short-term results with this tactic appear promising (N Engl J Med2001;344:472).2. A second rationale for STI is to "reimmunize" the patient to HIV in the hopes ofregaining immunologic control through a regenerated HIV-specific immuneresponse. This form of STI is usually studied in patients with optimal response toHAART, who have had no detectable plasma HIV RNA for 1 to 3 years in one oftwo settings: primary or early HIV infection, or chronic infection. In the chronicallyinfected group, STI is associated with virologic rebound involving thequasi-species that were found before HAART (J Infect Dis 2001;183:36) afterapproximately 2 to 8 weeks. Reappearance of HIV is accompanied by anaccelerated decrease in CD4 cell counts. These patients respond to reinstitution oftreatment, and some studies have found that treatment can be stopped repeatedlywith predictable response to retreatment. In vitro data may demonstrate improvedHIV-specific CTL responses, and in vivo data suggest that some patients havelonger mean replicative times correlating with improved in vitro HIV immuneresponses (J Infect Dis 2000;181;1264), but the number who have achievedlong-term virologic control without antiretroviral agents is low (8th CROI, Chicago,Ill., February 2001, Abstract 357). The experience is different for a small numberof patients who have had STI following HAART for primary HIV infection, wheresustained responses ascribed to CTL response have been achieved, such as inthe "Berlin patient" (N Engl J Med 1999;340:1683) and in 6 patients reported byRosenberg and associates (Nat Med 2000;407:523; 8th CROI, Chicago, Ill.,February 2001, Abstract 294).3. A third rationale for STI is simply to decrease cumulative exposure toantiretroviral agents, reducing toxicity and cost and improving quality of life. Anexample is the National Institutes of Health (NIH) study of "structured intermittenttherapy," in which patients were treated with HAART for 2 months followed by 1month off, or 1 week on and 1 week off (8th CROI, Chicago, Ill., February 2001,Abstracts 364 and 354).4. Some authorities recommend discontinuing antiretroviral drugs during the firsttrimester of pregnancy, since this is the time of fetal organ formation and also thetime of particularly poor gastrointestinal (GI) tolerance.Therapeutic drug monitoring (TDM): The purpose of TDM is to determineplasma levels of antiretroviral agents, usually to know whether drug levels aretherapeutic, and less frequently to explain possible toxicity or confirm adherence.This is not appropriate for NRTIs, since only intracellular levels are relevant; it isusually not appropriate for NNRTIs due to the long plasma half-life. The role of
    • Therapeutic drug monitoring (TDM): The purpose of TDM is to determineplasma levels of antiretroviral agents, usually to know whether drug levels aretherapeutic, and less frequently to explain possible toxicity or confirm adherence.This is not appropriate for NRTIs, since only intracellular levels are relevant; it isusually not appropriate for NNRTIs due to the long plasma half-life. The role ofTDM for PIs is debated. The main interest among enthusiasts is measuring troughlevels of PIs, primarily in recipients of single PI regimens, (ie, without RTV). Thisapplies especially to IDV, where trough levels at 8 hours are often subtherapeuticand peak levels above 10 mg/L are associated with nephrotoxicity (8th CROI,Chicago, Ill., February 2001, Abstract 730). Potential problems with TDM are thatindications are unclear, clinical benefit has not been clearly shown, the tests arenot readily available, and there appear to be enormous lab-to-lab variations whenanalyzing the same specimens (8th CROI, Chicago, Ill., February 2001, Abstract734).Trial Analysis: Results of most clinical trials are presented in "intent-to-treat"analysis or "as-treated" analysis using virologic end points of <500 c/mL or <50c/mL. In an "intent-to-treat analysis," the numerator is the number achieving thedesired end point, and the denominator is all patients randomized to that treatmentarm. Patients who discontinue the trial and those with missing data are counted asfailures. In an "as-treated analysis," the numerator is the number who achieve thedesired end point, and the denominator is the number continuing the trial to thattime point. In this analysis, patients who change therapy due to treatment failure,discontinue the trial due to side effects, or have other reasons for missing data areexcluded from the analysis. In trials of antiretroviral therapy, intent-to-treat analysisgives a better indication of "real world" issues, such as tolerability, convenience,and adherence, while as-treated analysis may better reflect relative potency. In areview of 17 HIV therapeutic trials, Hill and colleagues (6th CROI, Chicago, Ill.,February 1999, Abstract 394) showed that the mean percent achieving "virologicsuccess" was 81% by as-treated analysis using <500 c/mL as the therapeuticgoal, and 52% by intent-to-treat analysis. This represents a 29% difference (arange of 15% to 46% for individual studies), emphasizing the importance ofunderstanding the form of analysis before attempting to compare results acrosstrials.Undetectable virus or no detectable virus: This is the virologic goal of therapy,but the definition depends on the threshold of the assay used to determine plasmaHIV RNA levels. Common thresholds are 400 to 500 c/mL or 20 to 50 c/mL.Virologic failure: Generally defined as detectable HIV RNA with an assay thathas a threshold of detection of 20 to 50 c/mL after 24 to 36 weeks of initiatingtherapy or implementing a new regimen. The failure to reduce viral load by 1.5 to2.0 log10 at 4 weeks predicts virologic failure. HIV RNA levels >500 c/mL at >16 to24 weeks also predict virologic failure. The time it takes to reach the goal of <20 to50 c/mL depends on the baseline viral load as well as potency and adherence.Wild type virus: The predominant virus in a region or population of untreatedpatients. At present, the majority of strains are pan-sensitive, but this couldchange with time.
    • A. Antiretroviral Therapy for HIV-Infected Patients(http://www.hivatis.org, April 2001)The following DHHS guidelines for antiretroviral therapy are based on the document releasedin April 2001, with minor modifications. This document makes recommendations for: 1)indications to treat; 2) recommended starting regimens; 3) indications to change; and 4)regimens for salvage therapy. These four topics are presented in sequential order. In somecases, recommendations are also provided from the IAS-USA according to their consensusdated December 1999 (JAMA 2000;283:381).1. Indications for Antiretroviral Therapy DHHS Guidelines Table 4-2a: Indications to Initiate Antiretroviral Therapy -- DHHS Guidelines (http://www.hivatis.org, July 1, 2001) Clinical CD4 Cell Count Plasma HIV RNA Recommendation Category Symptomatic Any value Any value Treat (AIDS or severe symptoms) Asymptomatic Any value Any value Treat AIDS Asymptomatic CD4 cell count 200 Any value Treatment should usually be offered; to 350 cells/mm3 controversy exists for patients with viral load <20,000 c/mL due to low probability of AIDS-defining diagnosis within 3 years. Asymptomatic CD4 cell count >30,000 (bDNA) or Some experts would treat, since viral load at >350/mm3 >55,000 (RT-PCR) this threshold predicts a 3 year risk of AIDS in 30% despite high baseline CD4 cell count. Some would defer therapy and monitor CD4 cell count. *Strength of recommendation depends on prognosis ( Table 4-3) and patient readiness. Note: These recommendations are more conservative than prior DHHS guidelines based on the following observations: 1) HIV cannot be cured with currently available antiretroviral agents; 2) therapeutic trials have not been done that will determine efficacy with interventions based on CD4 cell counts >200/mm 3 ; 3) retrospective analyses of cohorts indicate that a CD4 threshold of 200/mm3 is too late, but the proper threshold above this level is unknown; 4) antiretroviral therapy is associated with substantial toxicity and adherence problems (Lancet 2000;355:2147; Ann Intern Med 2000;132:306). These recommendations generally define a group at 15% risk for an AIDS-defining diagnosis within 3 years. 4-2b: Indications for the Initiation of Antiretroviral Therapy - IAS-USA Recommendations (JAMA 2000;283:381). Viral Load (c/mL) CD4 Cell Count <5,000 5,000 to >30,000 (cells/mm 3 ) 30,000 <350 Treat Treat Treat 350 to 500 Consider Treat Treat
    • 350 to 500 Consider Treat Treat>500 Defer Consider TreatTable 4-3: Probability of an AIDS-Defining OIWithin 3 Years in the Absence ofAntiretroviral Therapy Based on BaselineCD4 Count and Viral Load. Data from MACS(Mellors J, et al. Ann Intern Med1997;126:946)CD4 Cell Count <350 % AIDS-defining ComplicationViral load n 3 years 6 years 9 years(RT-PCR)* 1500-7000* 30 0 18.8 30.6 7000-20,000 51 8.0 42.2 65.6 20,000-55,000 73 40.1 72.9 86.2 >55,000 174 72.9 92.7 95.6CD4 Cell Count 350-500Viral load n 3 years 6 years 9 years(RT-PCR)* 1500-7000 47 4.4 22.1 46.9 7000-20,000 105 5.9 39.8 60.7 20,000-55,000 121 15.1 57.2 78.6 >55,000 121 47.9 77.7 94.4CD4 Cell Count >500 1500-7000 180 2.3 14.9 33.2 7000-20,000 237 7.2 25.9 50.3 20,000-55,000 202 14.6 47.7 70.6 >55,000 141 32.6 66.8 76.3*Plasma HIV RNA levels in c/mL using RT-PCRNote: The recommendations of the DHHS Panel fortherapy of asymptomatic patients define a group with therisk for an AIDS-defining complication in the absence oftherapy of about 6% at 3 years, 25% at 6 years, and 50%at 9 years.
    • 2. Recommended Starting Regimens Table 4-4a: Initial Regimen - DHHS Guidelines (One from column A and one from column B in the preferred category) Column A Column B Preferred EFV d4T/3TC IDV AZT/ddI NFV AZT/3TC RTV/SQV d4T/ddI* RTV/IDV ddI/3TC LPV/RTV Alternative ABC AZT/ddC APV DLV NVP RTV SQV (FTV) NFV/SQV (FTV) No recommendation HU (insufficient data) RTV/APV RTV/NFV Not recommended SQV (Invirase) ddC/ddI ddC/d4T ddC/3TC AZT/d4T *The combination ddI/d4T should be avoided in pregnant women due to the risks for lactic acidosis and hepatoxicity. Table 4-4b: Initial Regimen - IAS-USA (JAMA 2000;283:381) Preferred: 2 nucleosides and a PI 2 nucleosides and 2 PIs 2 nucleosides and an NNRTI Under evaluation: 3 nucleosides 2 NRTIs + PI + NNRTI
    • a. Factors that influence probability of prolonged viral suppression usingregimens that are strongly recommended:Adherence: Obvious but critical, as demonstrated in a study that demonstrated astrong correlation between virologic response at an average follow-up period of 6months and adherence as monitored by Medication Event Monitoring System(MEMS) devices (Ann Intern Med 2000;133:21).Table 4-5: Correlation BetweenAdherence and VirologicResponse to HAARTAdherence to HAART* Viral Load <400 c/mL>95% adherence 78%90% to 95% adherence 45%80% to 90% adherence 33%70% to 80% adherence 29%<70% adherence 18%*Number of doses prescribed/number takenBaseline CD4 cell count: A relatively high CD4 cell count (>200/mm3) issometimes, but not invariably, associated with a superior viral response, and aCD4 cell count <50/mm3 has a relatively poor probability of a good virologicresponse (J Infect Dis 1999;180:659; Arch Intern Med 2000;160:1323). Review ofthe Moore Clinic database of patients in the Johns Hopkins AIDS Service showedan inverse correlation between baseline CD4 cell count and probability ofachieving a viral load <500 c/mL with HAART (Arch Intern Med 2000;160:1323):Table 4-6: Correlation BetweenBaseline CD4 Cell Count and VirologicResponse: Johns Hopkins Moore Clinic Viral Load <400Baseline CD4 Number c/mL(cells/mm 3 ) Ever >6 months>350 176 81% 43%200 to 350 125 74% 34%<200 326 65% 28%Similar results were noted with analysis of four protocols using IDV/AZT/3TC. Theprobability of achieving viral load <50 c/mL at 52 weeks with CD4 cell counts>500, 50-400, or <50 were 80%, 70%, and 45%, respectively (7th CROI, SanFrancisco, Calif., February 2000, Abstract 521).Baseline viral load: Most studies demonstrate a direct correlation between
    • Similar results were noted with analysis of four protocols using IDV/AZT/3TC. Theprobability of achieving viral load <50 c/mL at 52 weeks with CD4 cell counts>500, 50-400, or <50 were 80%, 70%, and 45%, respectively (7th CROI, SanFrancisco, Calif., February 2000, Abstract 521).Baseline viral load: Most studies demonstrate a direct correlation betweenbaseline viral load and probability of achieving viral suppression to <50 c/mL or<500 c/mL (AIDS 1999;13:1873; Clin Infect Dis 1999;29:75; Arch Intern Med2000;160:1323). In ACTG 175, a regimen of two NRTIs achieved a viral load <500c/mL in approximately half of patients with baseline viral loads of <10,000 c/mL.Most studies show that even some recommended regimens (two NRTIs + PI) areless effective in patients with a baseline viral load >100,000 c/mL; this was not thecase in initial studies using two NRTIs plus either EFV or LPV/RTV. The baselineviral load also predicts time required to reach undetectable virus (7th CROI, SanFrancisco, Calif., February 2000, Abstract 520).Prior exposure to antiretroviral agents: Multiple studies demonstrate a reversecorrelation between response and the extent of prior antiretroviral therapy withregard to number of agents, number of classes, and duration of treatment. In theSwiss Cohort study (Lancet 1999;353:863), for example, the probability ofachieving a viral load <500 c/mL with HAART therapy was 91% in treatment-naïvepatients compared with 75% in treatment-experienced patients. Among patientswho achieved undetectable virus, the probability of maintaining a viral load <500c/mL at 2 years was 80% for treatment-naïve patients compared with 62% fortreatment-experienced patients. The conclusion of many authorities is that theinitial regimen is the most important regimen because it is associated with thegreatest probability of achieving prolonged viral suppression (J AIDS2000;24;115).Nadir of viral load: Multiple studies demonstrate that the nadir plasma HIV RNAlevel strongly predicts the durability of response and in fact may be the single mostimportant predictor of a durable response.Rapidity of viral load response: The trajectory of the viral load responsepredicts the nadir plasma HIV RNA level and consequently predicts the durabilityof HIV response. Expectations are that treatment-naïve patients treated withHAART will have a viral load <400 c/mL at 12 weeks and <50 c/mL at 16 to 24weeks. In ACTG 320 the viral load response at 4 weeks strongly predictedlong-term viral suppression. Thus, clinical and viral load evaluation at 4 to 8 weekspermits an estimate of the probability of viral suppression and affords anopportunity for enhanced counseling on adherence (AIDS 2000;14:971). Thetrajectory of the virologic response has less predictive value in patients receiving"salvage" or "rescue" regimens.b. Regimens: Preferred regimens based on antiviral efficacy may be defined byclinical trial data showing a viral load <50 c/mL at >24 weeks for >40% ofparticipants by intent-to-treat analysis. A number of regimens achieve this goal intreatment-naïve patients. Characteristic features of these regimens are the use ofat least three drugs with a backbone of two nucleoside analogs combined with aPI or NNRTI (Table 4-4). (Note: These regimens should not be compared byoutcome due to differences in enrollment criteria, patient characteristics, extent ofadherence, etc.)Table 4-7: Relative Merits of Early Therapy and Delayed TherapyAdvantages of Early Therapy Advantages of Delayed TherapyControl viral replication Poor quality of life with treatment
    • Control viral replication Poor quality of life with treatmentPrevent progressive immune deficiency Earlier drug resistance if not fully effectiveBetter tolerability of drugs Limit future drug optionsReduce viral transmission Long-term drug toxicity Duration of effectiveness is unknown Risk for transmission of resistant strainsTable 4-8: Relative Merits of Antiretroviral Treatment RegimensRegimen Advantage Disadvantage2 NRTIs + PI Standard Cross-resistance among PI Extensively studied Inconvenience: BID or TID Durability >3 years (Merck 035 trial) regimens + food requirements Genetic barrier to resistance Toxicity: GI intolerance NNRTI-sparing Metabolic abnormalities Agent-specific adverse drug reactions (ADRs)2 NRTIs +NNRTI EFV appears comparable to Cross-resistance among NNRTIs PI-containing regimens with regard to Toxicity viral load response CNS (EVF) Durability (>2 years) Rash PI-sparing Lipid abnormalities (EFV) Pharmacologic barrier to resistance Hepatotoxicity (NVP) Good CNS penetration Possible decrease in potency Convenience of qd dosing (EFV) with high baseline viral load (NVP, DLV)ABC + 3TC +AZT PI- and NNRTI-sparing May have suboptimal response Simplicity of single pill BID with high baseline viral load Potential for extensive NRTI resistance Hypersensitivity reactions (ABC) Possible increase in mitochondrial toxicity2 NRTIs + PIs Pharmacologic benefit with reduced Cross-resistance among PIs doses and longer dosing intervals Toxicity: GI intolerance (regimen dependent) Metabolic abnormalities Increased potency (?) Agent-specific ADRs Improved tolerability Complex drug interactions with multiple agents2 NRTIs + PI +NNRTI Increased potency (?) Risk resistance to all 3 classes Reduced probability of resistance (?) Toxicity: ADRs of all 3 classes Complex drug interactions with multiple agentsPI + NNRTI Good potency Limited experience
    • PI + NNRTI Good potency Limited experience Avoid mitochondrial toxicity3. When to Change TherapyThe goal of therapy is to reduce HIV RNA to as low a level as possible for as longas possible, preferably using antiretroviral regimens that preserve future options,are relatively free of side effects, and are tailored to individual patient needs foradherence.Analysis of virologic results from many studies indicates that the post-treatmentviral load nadir is the best predictor of the durability of a sustained viral response.Optimal results are achieved with undetectable virus using an assay with athreshold of 20 to 50 c/mL. Studies show that <5% of all AIDS-definingcomplications occur in patients with a viral load of <5,000 c/mL, suggesting thatthresholds that define virologic failure and clinical failure may be different (AIDS1999;13:1035). However, the assumption is that virologic failure will eventuallylead to clinical and immunologic failure. Unfortunately, clinical studies show thatonly 15% to 30% of patients in most urban clinics achieve a sustained level of <20to 50 c/mL (Ann Intern Med 1999;131:18; AIDS 1999;13:F35), and the HIV Costand Services Utilization Study Consortium (HCSUS) study suggests that onlyabout 28% of persons in the United States who are receiving HIV care have a viralload <500 c/mL. Based on these observations, most authorities consider areduction to <20 to 50 c/mL to be the ultimate goal of therapy, but this may beunrealistic in many patients. More importantly, the attempt to achieve unrealisticvirologic responses may severely limit future therapeutic options due to theevolution of resistance.The probability of achieving the goal of <20 to 50 c/mL with HAART intreatment-naïve patients can be crudely predicted by the slope of the decay inplasma HIV RNA levels, which should show a decrease of 1.5 to 2.0 log10 c/mL at4 weeks, <500 c/mL by 12 weeks, and <50 c/mL at 16 to 30 weeks. The timerequired to reach undetectable levels correlates with the initial viral load, with anaverage of 73 days to <50 c/mL in one study (7th CROI, San Francisco, Calif.,February 2000, Abstract 520). Nevertheless, it is important to understand that thetime to achieve these nadir viral load thresholds depends to a large extent on thebaseline plasma HIV RNA level as well as the potency of the regimen andadherence to it. Once the goal of therapy has been achieved, therapy should becontinued indefinitely with monitoring of HIV RNA levels at 2- to 3-month intervalsand CD4 cell counts at 3- to 6-month intervals. The following guidelines apply:Indications to change therapy: The major goal of antiretroviral therapy is viralsuppression as indicated by HIV RNA levels. Changes based on inadequatevirologic response should be confirmed using at least two viral load measurementsat a time of clinical stability, bearing in mind that the 95% confidence interval forthe test is about 3-fold. Therapeutic regimens may also require change due toADRs or the complexity of the regimen, which may threaten adherence. Priorstudies indicate that drug toxicity accounts for 30% to 50% of regimen changes,and virologic failure accounts for most of the rest (J AIDS 2000;24:115; AIDS2000;14:499).
    • the test is about 3-fold. Therapeutic regimens may also require change due to ADRs or the complexity of the regimen, which may threaten adherence. Prior studies indicate that drug toxicity accounts for 30% to 50% of regimen changes, and virologic failure accounts for most of the rest (J AIDS 2000;24:115; AIDS 2000;14:499). CD4 cell counts: The CD4 response is generally a mirror image of the HIV RNA decay curve, with increases that average 100 to 200/mm 3 in the first year after complete virologic suppression. Subsequent increases are more gradual but usually continuous. The lack of a CD4 response despite viral suppression is sometimes considered an indication to change therapy, but data to support this strategy are largely absent. The development of HIV-associated complications despite good viral suppression is usually not considered grounds for changing the antiretroviral regimen. Causes of virologic failure: Inadequate virologic response is ascribed to: 1) lack of adherence; 2) reduced potency of the regimen; 3) pharmacologic failure due to reduced drug delivery to the site of infection (due to absorption, protein binding, and drug interactions); and 4) resistance. In general, most of the failure in the first 24 weeks of treatment using recommended HAART regimens in treatment-naïve patients is due to lack of adherence or inadequate potency, and most late failures that follow good virologic response are due to resistance. Changes due to ADRs: An attempt should be made to use a regimen with equal potency if virologic success was achieved. If the offending agent is unclear or GI toxicity precludes adherence, it is appropriate to suspend all treatment and then restart a modified regimen. In patients who may be experiencing the ABC hypersensitivity reaction, if possible, this drug should be discontinued and not restarted.4. New Regimen Selection: What to Change to: Changes in therapy can be classified into three categories: a) changes due to toxicity, including intolerance, lipodystrophy, and other ADRs; b) changes due to inconvenience of regimen; and c) changes due to virologic failure, which may reflect nonadherence, lack of potency, pharmacologic issues, or resistance. Guidelines are summarized below. Guidelines for Changing Antiretroviral Regimen (Modified from DHHS Guidelines, April 2001) When change is due to a single viral load determination, confirm with repeat test. Changes based on ADRs or intolerance can be made with single agent substitution, provided the patient has an appropriate virologic response to the original regimen. Changes based on virologic failure are often based on resistance test results and history of prior exposures. Empiric decisions without resistance testing after 24 to 36 weeks of therapy should usually involve selection of a completely new regimen unless for intensification. Some experts add drugs to intensify antiretroviral potency if the viral load decline is judged to be suboptimal at 8 to 16 weeks. This makes sense, but supporting data from trials are scant.
    • involve selection of a completely new regimen unless for intensification. Some experts add drugs to intensify antiretroviral potency if the viral load decline is judged to be suboptimal at 8 to 16 weeks. This makes sense, but supporting data from trials are scant. Patients with virologic failure and limited options may do best with continuation of regimen that shows only partial viral suppression. Multiple studies show that even patients with complete virologic failure derive clinical benefit, presumably due to altered HIV fitness (replicative capacity) or partial viral suppression (Lancet 1998;351:723; Lancet 1999;353:363; N Engl J Med 2001;344:472). Patients who fail HAART often require regimens containing two PIs or drugs from all three classes. Resistance tests are valid indicators of resistance only to drugs being taken at the time the test is performed or within approximately 2 weeks of discontinuation. Resistance should be suspected for drugs given previously during sustained periods with virologic failure. Expertise is a critical component of selecting regimens based on empiric decisions using the drug exposure history and in the interpretation of resistance tests. In making empiric decisions, assume partial cross-resistance for NNRTIs and for all PIs after failure of RTV, IDV or SQV; assume partial cross-resistance after failure of APV or LPV. Many think that NFV retains future PI options better than other PIs.Management of class ADRs with switch therapy: Guidance for regimenchanges due to class ADRs are largely based on data that are preliminary ornonexistent; hyperlipidemia may improve with change to two NRTIs + NVP or AZT+ 3TC + ABC (Trizivir); lipodystrophy is difficult or impossible to reverse withchanges in antiretroviral regimens; many experts conclude that fat atrophy is dueto d4T, ddI, or AZT (in that order) and fat accumulation is due to PIs (no clearlydefined order of agents); lactic acidosis is ascribed to NRTIs, primarily d4T, ddIand AZT (in that order); management recommendations include avoidance ofthese agents or use of a non-NRTI regimen (IDV + EFV, RTV + SQV, LPV/RTV +APV, LPV/RTV + EFV, AMP + RTV + EFV); enhanced bleeding in patients withhemophilia is attributed to PIs, but supporting data on the validity of theassociation or specific agents involved are sparse; hepatotoxicity is seen with allantiretroviral agents, more with RTV than with other PIs is more common withNVP compared to other NNRTIs; osteonecrosis may occur frequently withHAART, and importance is limited to a small fraction with avascular necrosis;management guidelines with respect to regimen changes are nil.Table 4-9: Recommendations for Changing Therapeutic Regimen (Modifiedfrom IAS-USA Recommendations, JAMA 2000;283:381;JAMA 2000;283:2417)Clinical Presentation RecommendationsToxicityVirologic success Viral load above target before 8 to Change offending drug
    • Viral load above target before 8 to Change offending drug16 weeks Viral load above target after 8 to Change entire regimen or use resistance testing to16 weeks guide drug selectionVirologic failure Viral load above target at 8 to 16 Continue regimen, check adherence and considerweeks intensification Viral load above target after 24 to Change entire regimen, use resistance testing, or36 weeks intensify Virologic "escape" after good Change entire regimen, use resistance testing, orsuppression intensifyEmpiric changes in NRTIs: The options may be limited by prior exposures ortoxicity. The best decisions are based on resistance test results combined withhistorical data, especially with evolving data concerning cross-resistance betweenAZT and other nucleosides. The following is a crude guide for decisions based onhistorical data only: AZT + 3TC ddI + d4T AZT + ddI d4T + 3TC d4T + ddI AZT + 3TC + ABC d4T + 3TC AZT + ddI + ABC AZT + ddC d4T + 3TC, d4T + ddI, ddI + 3TCNote: Studies of ABC in salvage regimens show little or no virologic response thatcan be independently ascribed to this agent in patients with extensive previousNRTI exposure, presumably due to cross-resistance but ABC may work afternon-AZT-containing regimens, with low-level AZT resistance, and it may be usefulfor intensification.Emperic changes in PI-containing regimens: a. NNRTIs in patients without prior exposure to this class b. Dual PIs, usually RTV/SQV, RTV/IDV, RTV/APV, NFV/SQV, or LPV/RTV with the following caveats: a) PI salvage from PI-containing regimens is most likely to be successful only if the viral load is relatively low (<15,000-30,0000 c/mL) and preferably <5,000 c/mL) when the switch is made; b) IDV and RTV demonstrate nearly complete cross-resistance, so the main reason to combine them is to potentiate IDV levels; and c) some data suggest that PIs are more likely to be effective following NFV or APV therapy than after failure of other PIs. NNRTI-containing regimens should be empirically changed to a PI-containing regimen. APV and LPV/RTV may be more active vs HIV strains resistant to other PIs. c. Triple-class regimens: The risks associated with triple-class regimens are exposure to all classes with the consequent impact on options if there is virologic failure with resistance; the lack of information about the pharmacology of some drug combinations; and sparse clinical trial data. Nevertheless, these may represent the most effective regimens in patients who fail alternative treatments.Empiric changes in NNRTI regimens:
    • virologic failure with resistance; the lack of information about the pharmacology of some drug combinations; and sparse clinical trial data. Nevertheless, these may represent the most effective regimens in patients who fail alternative treatments. Empiric changes in NNRTI regimens: a. PI regimen in patients who are not resistant to these drugs. b. Some patients who fail with only a 181 condon mutation will respond to EFV. Table 4-10: Suggested Empiric Regimens for Patients Who Failed Antiretroviral Therapy Prior Regimen New Regimen 2 NRTIs + PI 2 new NRTIs plus NNRTI or Dual PIs (RTV + SQV, RTV + IDV, NFV + SQV, RTV + APV, LPV/RTV or Triple-class regimen with 1 or 2 NRTIs plus NVP or EFV plus 1 or 2 PIs 2 NRTIs + NNRTI 2 new NRTIs + 1 or 2 PIs ABC + AZT + 3TC 2 new NRTIs (ddI/d4T) + either PI or NNRTI 2 NRTIs 2 new NRTIs + PI or NNRTI Selection based on resistance testing: Initial results from trials in which rescue regimens were selected by genotypic resistance test results compared with "standard of care" show two major benefits compared with decisions based on antiretroviral therapy history: 1) virologic outcome at 16 to 24 weeks appears to be superior and 2) the number of drugs changed is reduced (CPCRA 046, 6th CROI, Chicago, Ill., February 1999, Abstract LB8; 7th CROI, San Francisco, Calif., February 2000, Abstract 237; Lancet 1999;353:2195; AIDS 1999;13:1861; J Infect Dis 2001;183:401). Nevertheless, these studies have consistently shown that the benefit of resistance testing compared with decisions based on history is modest and often not statistically significant. Critical issues are adherence, expertise in interpreting resistance tests, and expertise in making decisions based on drug exposure history. Top of Page | Next page -- Recommendations for Antiretroviral Therapy in PregnancyCopyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rightsreserved.* Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained inthis site because no single reference or service can take the place of medical training, education, and experience. Consumers arecautioned that this site is not intended to provide medical advice about any specific medical condition they may have or treatmentthey may need and they are encouraged to call or see their physician or other health care provider promptly with any health relatedquestions they may have.
    • Go to a Chapter Table of Contents Natural History and Classification Tests Disease Prevention Antiretroviral Therapy Management of Opp Infections Drugs: Guide to Information Systems Review HIV in CorrecIV. Antiretroviral TherapyRecommendations for Antiretroviral Therapy Goals of Therapy Terms and Concepts Antiretroviral Therapy for HIV Infected Patients Recommendations for Antiretroviral Therapy in Pregnancy Postexposure Prophylaxis for Health Care Workers Postexposure Prophylaxis for Sexual Contact or Needle SharingAntiretroviral Agents Nucleoside Analogs Non-nucleoside Reverse Transcriptase Inhibitors (NNRTI) Protease Inhibitors Class Adverse Reactions to Antiretroviral AgentsTables Table 4-16: Antiretroviral Drugs Approved by FDA for HIV Table 4-20: Drugs That Should Not be Used with Protease Inhibitors or NNRTIs* Table 4-21: Drug Interactions Requiring Dose Modifications or Cautious Use Table 4-22: Drug Interactions: Protease Inhibitors and Non-Nucleoside Reverse Transcriptase Inhibitors Effect of Drug on Levels (AUCs)/Dose Table 4-27: HIV-Related Drugs with Overlapping Toxicities Table 4-28: Dosing of Antiretroviral Agents in Renal and Hepatic Failure Table 4-29: Characteristics of Antiretrovirals During Dialysis I. Recommendations for Antiretroviral TherapyBased on the recommendations of the DHHS/Kaiser Family Foundation as of May 2001; (DHHSPanel on Clinical Practices for Treatment of HIV Infection Guidelines for Use of AntiretroviralAgents in HIV-infected Adults and Adolescents); available at http://www.hivatis.org. Print copiesmay be obtained from HIV/AIDS Treatment Information Service, P.O. Box 6303, Rockville, MD20849-6303; telephone: 800-448-0440.B. Recommendations for Antiretroviral Therapy in Pregnancy
    • 1. ACTG 076 ACTG 076 showed that AZT reduced the rate of perinatal transmission from 22.6% to 7.6% (N Engl J Med 1996;335:1621). Multiple uncontrolled studies have confirmed the benefit of AZT in reducing perinatal transmission (J Infect Dis 1995;172:353; Clin Infect Dis 1995;20:1321) and subsequent surveillance studies in the United States showed substantial declines in the rates of perinatally acquired HIV that accompanied use of AZT in pregnant women (MMWR 1997;46:1986).2. Subsequent data: The current PHS recommendations (January 24, 2001, Revised Guidelines, available at http://www.hivatis.org) are based on the philosophy that "pregnancy" per se should not preclude use of optimal therapeutic regimens. However, the choice of drug is subject to unique considerations, including potential changes in dosing requirement due to the physiologic changes associated with pregnancy and the potential effects of the antiretroviral drugs on the fetus and newborn." In essence, all pregnant women are candidates for antiretroviral therapy regardless of the CD4 cell count and viral load. The following points provide the rationale for the current guidelines: Viral load: Pregnant women should be treated with antiretroviral agents selected to reduc viral load to as low a level as possible regardless of the initial CD4 cell count and viral load, since low maternal viral load confers dramatic protection to the unborn child. Specifically, a large study showed that the rate of perinatal transmission with viral load >100,000 c/mL was 41%; with 1000 to 10,000 c/mL it was 17%; and with <1000 c/mL it was zero (N Engl J Med 1999;341:394). Analysis of ACTG 185 showed similar results (N Engl J Med 1999;341:385). Despite these findings, it should be emphasized that there is no viral load that can be regarded as safe, since other factors also play a role (AIDS 1999;13:1377; AIDS 1999;13:407; J Infect Dis 1999;179:590). AZT: This drug should be included when possible to prevent perinatal transmission since AZT and NVP are the only antiretroviral agents that have established merit in reducing perinatal transmission. AZT appears to reduce perinatal transmission independently of the viral load (N Engl J Med 1996;335:1621; Lancet 1999;354:156) and also seems effective even when the maternal HIV strain shows AZT resistance (J Infect Dis 1998;177:557). The latter finding is somewhat controversial (AIDS 2000;14:263). Analysis of ACTG 076 showed that AZT significantly reduces perinatal transmission even when the baseline vira load is <1000 c/mL (J Infect Dis 2001;183:539). NVP: NVP is the only agent other than AZT that has established merit in preventing perinatal transmission. HIVNET 012 was a randomized trial conducted in Africa comparin NVP (200 mg by mouth given to the mother during labor and a single 2 mg/kg dose given within 72 hours to the infant) vs AZT (600 mg at onset of labor followed by 300 mg every 3 hours until delivery to mother and 400 mg/kg/day x 7 days to the infant). The NVP arm showed a significant reduction in perinatal transmission (13.1% vs 21.5%). However, analysis of HIVNET 012 participants given NVP at 6 weeks postpartum showed NVP resistance mutations (AIDS 2000;14:F111). Four of 7 with these mutations lost them at 13 to 18 months. The implications of these observations are unclear. Cesarean section: C-section has established efficacy in reducing perinatal transmission when maternal viral load exceeds 1000 c/mL. A meta-analysis of 15 studies with 8533 mother-infant pairs showed the following rates of perinatal transmission: no AZT + vagina delivery - 19%; no AZT + C-section - 10%; AZT + vaginal delivery - 7%; AZT + C-section 2% (N Engl J Med 1999;340:977). A study by the European Mode of Delivery Collaboration randomly assigned patients to vaginal delivery vs C-section. The C-section group had a perinatal transmission rate of 3/170 (1.8%) compared with 21/2001 (10.5%) in the vaginal delivery group. However, no one has examined the benefit of C-section in women receiving HAART or in women with a viral load <1,000 c/mL. Another concern is that there is an increased risk associated with C-section in women with low CD4 cell
    • 2% (N Engl J Med 1999;340:977). A study by the European Mode of Delivery Collaboration randomly assigned patients to vaginal delivery vs C-section. The C-section group had a perinatal transmission rate of 3/170 (1.8%) compared with 21/2001 (10.5%) in the vaginal delivery group. However, no one has examined the benefit of C-section in women receiving HAART or in women with a viral load <1,000 c/mL. Another concern is that there is an increased risk associated with C-section in women with low CD4 cell counts (AIDS 196;9:913; JAMA 1999;281:1946; Lancet 1999;354:1612; Obstet Gynecol 1999;94:942; Obstet Gynecol 1998;92:945; Obstet Gynecol 1998;92:507; J AIDS 2001;26:236). The risk is greatest for C-section performed at the time of labor or in a patient with ruptured membranes, but risks are also increased with elective C-section. This risk is increased further with malnutrition, obesity, smoking, genital infection, low socioeconomic status, prolonged labor, and membrane rupture. The major complications noted in these reports were wound infections, pneumonia, and endometritis. Safety of antiretroviral therapy: The data to date support the safety of antiretroviral agents in pregnancy except for ddI + d4T, EFV, and HU (J AIDS 2000;25:306). The combination of ddI + d4T should be avoided due to reports of three maternal deaths ascribed to lactic acidosis and/or hepatotoxicity. EFV should be avoided in the first trimester due to teratogenic effects when given to primates. HU is unsafe in pregnancy and carries a class D FDA rating (Table 4-11). A report from France suggested mitochondrial toxicity with neurologic sequelae in children exposed to AZT in utero (Lancet 1999;354:1084). Evaluation of 20,000 infants exposed to AZT in utero has not confirmed the report and showed no evidence of immunologic, cardiac, oncogenic, neurologic, or immunologic consequences (N Engl J Med 2000;3:805). Pharmacology: There are limited data on the pharmacokinetics of antiretroviral drugs in pregnancy. Normal profiles are noted with AZT, 3TC, and NVP. Preliminary data with SQV show a substantial reduction in plasma levels, suggesting the need for therapeutic monitoring, or RTV boosting, or both. This concern may apply to the PI class. First trimester: The safety of antiretroviral agents during the first trimester is sometimes questioned, since this is the time of fetal organ formation. There are no data to support or refute these concerns. Some experts recommend a delay in starting antiretroviral agents or suspending treatment during the first trimester. This involves a risk-benefit decision. Tolerability of antiretroviral agents: Pregnant women may experience unusual difficulty in tolerating antiretroviral regimens due to nausea and vomiting, especially during the first trimester. All antiretroviral drugs should be discontinued during periods of poor intolerance, and an attempt should be made to identify the best-tolerated regimen with established potency. Glucose intolerance is common during pregnancy and is also a complication of HAART; this indicates the need for careful glucose monitoring. Time of perinatal transmission: Most perinatal transmission occurs during delivery so this time should be the subject of the most intensive efforts (Am J Obstet Gynecol 2000;183:638). Nevertheless, AZT-containing regimens should be started at or before 28 weeks gestation; later initiation is associated with increased rates of perinatal transmission (N Engl J Med 2000;343:982). The postpartum component of the ACTG 076 protocol has an established contribution to efficacy as well. Breast feeding: The risk of HIV transmission with breast feeding is 16% (JAMA 2000;283:1167; Lancet 1992;340:385; JAMA 2000;283:1175). The risk appears greatest in the first 4 to 6 months (JAMA 1999;282:744). Breast feeding is consequently discouraged for HIV-infected women in the developed world; the issue is more complex in the developing world (JAMA 2000;238:1167).3. Guidelines - DHHS (http://www.hivatis.org, April 2001) ACTG 076 protocol Antepartum: AZT 300 mg bid or 200 mg tid from week 14 to delivery Intrapartum: AZT IV 2 mg/kg 1st hour, then 1 mg/kg/hour until delivery Postpartum: AZT syrup, 2 mg/kg q6h (or 1.5 mg/kg q6h IV) x 6 weeks for the infant HIV Infected Women Without Prior Therapy
    • HIV Infected Women Without Prior Therapy Presents in early pregnancy (<36 weeks): Viral load >1,000 c/mL: HAART regardless of CD4 cell count with: 1) Inclusion of AZT according to ACTG 076, and 2) possible delay until 10 to 12 weeks gestation. Viral load <1,000 c/mL: AZT monotherapy according to the 076 protocol, including a delay until 10 to 12 weeks gestation. Monitor viral load, CD4 cell count, and resistance tests as recommended for nonpregnant patients. At 36 weeks, inform patient of risks and benefits of C-section; encourage C-section if viral load is >1,000 c/mL. Presents in late pregnancy (>36 weeks): Initiate standard 076 protocol with AZT; encourage C-section at 38 weeks if viral load >1,000 c/mL. Presents in labor: Options are (in no particular order of priority): NVP 200 mg at onset of labor; infant-single dose of 2mg/kg at 48 hours AZT 600 mg PO at onset of labor, then 300 mg PO q3h until delivery plus 3TC 150 mg PO at onset of labor and 150 mg q12h until delivery; infant - AZT 4 mg/kg PO q12h plus 3TC 2 g/kg q12h x 7 days AZT 2 mg/kg IV, then 1 mg/kg/hour IV until delivery; infant - AZT 2 mg/kg PO q6h x 6 weeks (076 protocol) NVP + AZT as described above Presents postdelivery: 1) Initiate 6-week AZT protocol for infant, 2) evaluate infant for HIV infection when feasible, and 3) evaluate mother for indications for antiretroviral therapy.Treated Patient Early pregnancy - 36 weeks: Continue antiretroviral therapy with standard monitoring with three differences: 1) include AZT if tolerated and appropriate from a virologic standpoint, 2) avoid HU and avoid d4T + ddI, and 3) consider discontinuation of all antiretroviral agents during first trimester. >36 weeks: Continue antiretroviral therapy including all agents without interruption during delivery; inform patient of risks and benefits of C-section, encourage C-section at 38 weeks if viral load >1,000 c/mL.Cesarean Section C-section: If elective it should be done at 38 weeks. IV AZT should begin 3 hours before surgery; all other antiretrovirals should continue without interruption. Give antibiotic prophylaxis for C-section. C-section planned; but patient presents in labor: Initiate 076 protocol, intrapartum component.
    • C-section: If elective it should be done at 38 weeks. IV AZT should begin 3 hours before surgery; all other antiretrovirals should continue without interruption. Give antibiotic prophylaxis for C-section. C-section planned; but patient presents in labor: Initiate 076 protocol, intrapartum component. Rapid progression of labor: Vaginal delivery Long labor anticipated: Consider loading dose of AZT or oxytocin to expedite delivery.4. Antiretroviral Pregnancy RegistryCare providers with HIV-infected pregnant women should report cases of prenatal exposure tothe Antiretroviral Pregnancy Registry. This registry collects observational data, patients areanonymous, and the Registry obtains birth outcome data. The Registry can be contacted at: Antiretroviral Pregnancy Registry 115 N. Third St., Suite 306 Wilmington, NC 28401 TEL: 800-258-4263 or 910-251-9087 FAX: 800-800-1052 Table 4-11: Safety of Antiretroviral Agents in Pregnancy Antiretroviral FDA Placental Passage Long-term Animal Rodent Teratogen Drug Category* Newborn:Maternal Carcinogenicity Drug Ratio Studies AZT C Yes (human) [0.85] Positive (rodent, Positive (near lethal vaginal tumors) dose) ddC C Yes (rhesus) [0.3-0.50] Positive (rodent, Positive thymic lymphomas) (hydrocephalus at high dose) ddI B Yes (human) [0.5] Negative (no Negative tumors, lifetime rodent study) d4T C Yes (rhesus) [0.76] Not completed Negative (but sternal bone calcium decreases) 3TC C Yes (human) [~1.0] Negative (no Negative tumors, lifetime rodent study) ABC C Yes (rats) Not completed Positive (anasarca and skeletal malformations at 1000 mg/kg during organogenesis) SQV B Unknown Not completed Negative IDV C Yes (rats) ("significant" Not completed Negative (but extra in rats, low in rabbits) ribs in rats) RTV B Yes (rats) [mid-term Positive (rodent Negative (but fetus, 1.15; late-term liver adenomas and cryptorchidism in rats fetus, 0.15-0.64] carcinomas in male at maternally toxic mice) doses) NFV B Unknown Not completed Negative APV C Unknown Not completed Positive (thymic elongation; incomplete
    • APV C Unknown Not completed Positive (thymic elongation; incomplete ossification of bones; low body weight) NVP C Yes (human) [~1.0] Not completed Negative DLV C Yes (rats) [late-term Not completed Ventricular septal fetus, blood, 0.15; defect late-term fetus, liver, 0.04] EFV C Yes (cynomolgus Not completed Anencephaly; monkeys, rats, rabbits) anophthalmia; [~1.0] microphthalmia (cynomolgus monkeys) LPV/RTV C Unknown Not completed Negative (but delayed ossification and increase in skeletal variations in rats at maternally toxic doses) * See Pregnancy Categories. Top of Page | Next page -- Postexposure Prophylaxis for Health Care WorkersCopyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rightsreserved.* Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained inthis site because no single reference or service can take the place of medical training, education, and experience. Consumers arecautioned that this site is not intended to provide medical advice about any specific medical condition they may have or treatmentthey may need and they are encouraged to call or see their physician or other health care provider promptly with any health relatedquestions they may have.
    • Go to a Chapter Table of Contents Natural History and Classification Laboratory Tests Disease Prevention Antiretroviral Therapy Managem Opportunistic Infections Drugs: Guide to Information Systems Review CorrectionsIV. Antiretroviral TherapyRecommendations for Antiretroviral Therapy Goals of Therapy Terms and Concepts Antiretroviral Therapy for HIV Infected Patients Recommendations for Antiretroviral Therapy in Pregnancy Postexposure Prophylaxis for Health Care Workers Postexposure Prophylaxis for Sexual Contact or Needle SharingAntiretroviral Agents Nucleoside Analogs Non-nucleoside Reverse Transcriptase Inhibitors (NNRTI) Protease Inhibitors Class Adverse Reactions to Antiretroviral AgentsTables Table 4-16: Antiretroviral Drugs Approved by FDA for HIV Table 4-20: Drugs That Should Not be Used with Protease Inhibitors or NNRTIs* Table 4-21: Drug Interactions Requiring Dose Modifications or Cautious Use Table 4-22: Drug Interactions: Protease Inhibitors and Non-Nucleoside Reverse Transcriptase Inhibitors Effect of Drug on Levels (AUCs)/Dose Table 4-27: HIV-Related Drugs with Overlapping Toxicities Table 4-28: Dosing of Antiretroviral Agents in Renal and Hepatic Failure Table 4-29: Characteristics of Antiretrovirals During Dialysis I. Recommendations for Antiretroviral TherapyBased on the recommendations of the DHHS/Kaiser Family Foundation as of May 2001; (DHHS PClinical Practices for Treatment of HIV Infection Guidelines for Use of Antiretroviral Agents in HIV-Adults and Adolescents); available at http://www.hivatis.org. Print copies may be obtained from HITreatment Information Service, P.O. Box 6303, Rockville, MD 20849-6303; telephone: 800-448-04C. Postexposure Prophylaxis (PEP) for Health Care Workers(MMWR 2001;50[RR-1]).
    • 1. Risk for TransmissionA total of 23 studies of needle sticks among health care workers demonstrate HIV transmission6135 (0.33%) exposed to an HIV-infected source (Ann Intern Med 1990;113:740). With mucossurface exposure, there was one transmission in 1143 exposures (0.09%), and there were notransmissions in 2712 skin exposures. As of June 2000, there were a total of 56 health care wothe United States. who had occupationally acquired HIV infection as indicated by seroconversiocontext of an exposure to an HIV-infected source. There are an additional 132 health care workhad possible occupationally acquired HIV; these latter health care workers did not have documseroconversion in the context of an exposure. Of the 56 confirmed cases: 1) the major occupatwere nurses (23), laboratory technicians (20), and physicians (6); 2) all transmissions involvedbloody body fluid except for three involving laboratory workers exposed to HIV viral cultures; 3)exposures were percutaneous in 48, mucocutaneous in five, and both in two cases; and 4) to dthere are no confirmed seroconversions in surgeons and no seroconversions with exposures tosuture needle.A retrospective case-control study of needle-stick injuries from an HIV-infected source by the Cincluded 33 cases who seroconverted and 739 controls (MMWR 1996;45:468; N Engl J Med1997;337:1485). Results showed that risks for seroconversion included: 1) deep injury; 2) visibon the device; 3) needle placement in a vein or artery; and 4) a source with late-stage HIV infec(presumably reflecting high viral load). There was also evidence that AZT prophylaxis was assowith a 79% reduction in transmission rates. On the basis of this experience, revised preliminaryguidelines recommending more aggressive antiretroviral therapy were published in June 1996 (1996;45:468) and updated in 1997 (Am J Med 1997;102:117) and then updated again in 20012001;50:[RR-11]).2. Management (PHS Statement on the Management of Occupational Exposures to HIV and Recommendations for Postexposure Prophylaxis (MMWR 2001;50:[RR-11]) ). Occupational Exposure Management Resources: National Clinicians Postexposure Prophylaxis Hotline (HRSA, AETC, CDC) (availab at all times): 888-448-4911 or http://www.ucsf.edu/hivcntr Needlestick (UCLA): http://www.needlestick.mednet.ucla.edu Hepatitis hotline: 888-443-7232 or http://www.cdc.gov/hepatitis CDC Reporting (occupationally acquired HIV and PEP failure): 800-893-0485 FDA: Unusual or severe toxicity of antiretrovirals: 800-332-1088 or http://www.fda.gov/medwatch/index.html HIV/AIDS Treatment Information: http://www.hivatis.org3. Management of occupational exposure to HBV, HCV, and HIV (MMWR 2001;50:[RR-1]) Risk of Viral Transmission With Sharps Injury from Infected Source: Source Risk HBV (unvaccinated): Source HBeAg+ 37% to 62% - Source HBeAg 23% to 37% HCV 1.8%
    • HCV 1.8%HIV 0.3%HBV Postexposure Prophylaxis: This is unchanged from previous recommendations.Recommendations are based on the vaccine status of the healthcare worker, evidence ofserologic response, (anti-HBs levels >10 mIU/mL), and the source.Table 4-12: HBV Postexposure ProphylaxisVaccination Status of Features of SourceHealthcare Worker HBsAg Positive Source UnknownUnvaccinated HBIG* + vaccine series (3 doses) HBV vaccine (3 doses)Vaccinated Responder No Rx No Rx Non responder HBIG x 1 + vaccine series or HBIG x 2 Rx as source positive if high riskAntibody status Test for anti-HBsunknown Anti-HBs >10 mIU/mL -- no Rx Anti-HBs <10 mIU/mL -- HBIG x 1 + vaccine booster* HBIG=Hepatitis B Immune Globulin; dose is 0.06 mL/kg IM. Should be given as soon as possible and w7 days. Responder defined by antibody to HBsAg of >10 mIU/mL. HBIG + the vaccine series is preferred for non-responders who did not complete the 3 dose series; HBIGdoses is preferred if there were 2 vaccine series and no response.HCV Postexposure Prophylaxis: Risk: 1.8% with sharps injury from HCV infected source Source testing: anti-HCV; confirm positives as with RIBA Health care worker: Anti-HCV and ALT at baseline and at 4 to 6 months. HCV RNA may be tested at 4 to 6 weeks to detect acute HCV prior to seroconversion. All positive anti-HCV tests should be confirmed as with RIBA tests No prophylaxis with IG or with antiviral agents (interferon + ribavirin) is recommendedHIV Postexposure Prophylaxis: Recommendations are based on the type of exposureand the risk status of the source.Table 4-13: HIV Postexposure Prophylaxis for Percutaneous InjuriesExposure Status of Source Low risk* High risk*Not severe: Solid needle, superficial 2 drug PEP 3 drug PEPSevere: Large bore, deep injury, visible blood in device, 3 drug PEP 3 drug PEP
    • Severe: Large bore, deep injury, visible blood in device, 3 drug PEP 3 drug PEP needle in patient artery/vein * Low risk: Asymptomatic HIV or viral load >1,500 c/mL; High risk: Symptomatic HIV, AIDS, acute serocon and high viral load Concern for drug resistance: Initiate prophylaxis without delay and consult an expert. Consider 2 drug PEP if source is high risk for HIV or exposure is from an unknown source with HIV infec Table 4-14: HIV Post Exposure Prophylaxis for Mucous Membrane and Non-intact Exposures* Exposure Status of Source Low risk High risk Unknown Small volume Consider 2 drug PEP 2 drug PEP Usually no PEP; consider 2 drug (drops) Large volume 2 drug PEP 3 drug PEP Usually no PEP; consider 2 drug (major blood splash) * Non-intact skin = dermatitis, abrasion, wound Low risk = Asymptomatic or viral load <1,500 c/mL; High risk = acute seroconversion, high viral load. Consider if source has HIV risk factors or exposure from unknown source where HIV infected source is l Recommended regimens: 2 drug combinations AZT + 3TC 3TC +d4T d4T + ddI 3 drug combinations 2 nucleosides (above list) + IDV, NFV, EFV, ABC, RTV, FTV, APV, DLV, or LPV. Decisions should be made based in part on information about the source, including antiretroviral therapy, response to therapy, including viral load, and any data on HIV resistance testing. Decisions should not delay initiation of PEP, and modifications can be made after treatment has started.4. MonitoringTesting source: If there is no recent positive or negative serology, a rapid test is preferred, sinresults should be available in <10 minutes. Standard serologic tests may take 3 to 7 days, but anegative EIA screening assay is usually available in 24 to 48 hours and is adequate for the decdiscontinue PEP. Some states permit testing the source of a health care worker exposure withoinformed consent; about half require informed consent. If the source has had an illness compatacute HIV syndrome, testing should include plasma HIV RNA levels.Testing health care worker: HIV serology should be performed at the time of injury, and repeweeks, 3 months, and 6 months. There have been three health care workers who seroconvertemonths postexposure. This represents about 4% of confirmed seroconversions in health care w(Am J Med 1997;102:117). Most health care workers who seroconverted had symptomatic acusyndrome, usually 2 to 6 weeks postexposure.
    • Testing health care worker: HIV serology should be performed at the time of injury, and repeweeks, 3 months, and 6 months. There have been three health care workers who seroconvertemonths postexposure. This represents about 4% of confirmed seroconversions in health care w(Am J Med 1997;102:117). Most health care workers who seroconverted had symptomatic acusyndrome, usually 2 to 6 weeks postexposure.Caution: The health care worker should be advised to practice safe sex or abstain until serolognegative at 6 months postexposure. The greatest risk is the first 6 to 12 weeks.Time: PEP should be initiated as quickly as possible, preferably within 1 to 2 hours of exposureto 36 hours postexposure. The median time from exposure to treatment in 432 health care workHIV exposure from October 1996 to September 1998 was 1.8 hours (Infect Control Hosp Epid2000;21:780).Side effects: For health care workers who receive PEP, about 74% experience side effects, pnausea (58%), fatigue (37%), headache (16%), vomiting (16%), or diarrhea (14%). About 53%discontinue treatment before completion of the 4-week course due to multiple factors includingeffects of drugs (Infect Control Hosp Epid 2000;21:780).Pregnancy: There is evidence of carcinogenicity ascribed to AZT using 12 to 15x the standardrodents. The relevance of this experience to patients is unknown. Extensive experience with 20infants exposed to AZT in utero failed to reveal any clear evidence of toxicity. With regard to otagents, EFV and the combination of ddI and d4T should be avoided in pregnancy. Counselingcare workers with childbearing capacity should include a discussion of these risks and the limiteregarding safety of any antiretroviral agents, especially during the first trimester and the limitedof PIs in pregnant women. CDC guidelines state that pregnancy should no preclude PEP (MMW1998;47:1).Breast feeding: Consider temporary discontinuation of breastfeeding during antiretroviral theraConfidentiality: This is considered critical.Agent selection: AZT is advocated because it has been used extensively and has establishedfor preventing transmission. Safety in this setting appears well established, and efficacy appearabout 80%. AZT use in pregnancy suggests efficacy even when the implicated source strain shgenotypic resistance to AZT, although efficacy is reduced. Other agents in the standard PEP reare suggested based on enhanced antiretroviral potency and toxicity profile. NVP should be avdue to concerns about hepatoxicity. This drug also causes high rates of rash and occasional caStevens-Johnson syndrome. The CDC has issued a warning against NVP use for PEP based oreports of 12 cases of hepatotoxicity (one requiring a liver transplant) and 14 cases of severe srashes including 1 to 3 cases of Stevens-Johnson syndrome (MMWR 2001;49:1153). EFV cautoxicity and possible teratogenic effects in pregnancy. PIs are generally considered to be of equpotency; the prior preference for IDV and NFV was based on availability and experience at theCDC recommendations were written. LPV/RTV (Kaletra) may be an attractive choice due to polow probability of resistance, and tolerability. IDV + RTV may also be a more attractive option thas the sole PI. Anticipated or proven resistance in the source strain may influence decisions reagent selection in the health care worker. Tolerance is another important issue since most HCWexperience side effects, especially nausea, fatigue, and headache; these are sufficiently severerequire regimen change or discontinued treatment in about half.Resistance testing: Some advocate testing resistance of the source strain to facilitate drug sein the exposed health care worker. The obvious problem is the time required for test results andimportance of rapid institution of prophylaxis. Most authorities recommend that decisions be bathe drug history and viral load of the source. In a review of 52 patients who were the source ofoccupational exposures, 39% had major mutations conferring resistance (7th CROI, San Franc
    • Resistance testing: Some advocate testing resistance of the source strain to facilitate drug sein the exposed health care worker. The obvious problem is the time required for test results andimportance of rapid institution of prophylaxis. Most authorities recommend that decisions be bathe drug history and viral load of the source. In a review of 52 patients who were the source ofoccupational exposures, 39% had major mutations conferring resistance (7th CROI, San FrancCalif., February 2000, Abstract 469).Postexposure registry: The registry was closed effective June 30, 1999 (MMWR 1999;48:195. PEP: experience in the United States: Results of PEP Registry (Infect Control Hosp Epidim 2000;21:780) Period reviewed: October 1996 - December 1998 Number of injuries reviewed: 492 HIV status of source known to be positive: 258 (60%) Type of exposure: percutaneous 85% mucocutaneous 10% Fluid: Blood - 71% Bloody fluid - 13% HIV culture - 2.3% Time to initiate PEP antiretroviral therapy: 1.8 hours (median) Treatment: three drugs - 59%, two drugs - 36%, four drugs - 4% Side effects: any - 76%, nausea - 57%, fatigue - 38%, headache - 18%, vomiting - 16%, diarrh 14%; side effects with AZT + 3TC regimen - 63%; side effects with AZT/3TC/IDV - 83% Proportion who discontinued or modified treatment due to side effects: 54%6. Health care worker to patient transmission: This became a topical issue in 1990 with the Dr. Acer, a Florida dentist, who was identified as the source of HIV infection for six dental patie Intern Med 1992;116:798; Ann Intern Med 1994;121:886). The source of the virus was establis genetic sequencing (J Virol 1998;72:4537), but the mechanism of transmission was never esta This disclosure led to a series of "look backs," in which serologic tests were performed on over patients who received care from 59 health providers with known HIV infection. No transmission identified (Ann Intern Med 1995;122:653). Since this time there has been one additional case, a orthopedic surgeon in France who may have transmitted HIV infection to a patient during a tota replacement in 1992 (Ann Intern Med 1999;130:1).Management: The incident with the Florida dentist raised great concern about this issue and lerecommendation for review of practices by HIV-infected providers who "performed invasive proin a blind body cavity." It was felt that performing surgery in anatomical sites that could not be vwould be most likely to result in injuries, with the potential for patient exposure to provider bloodstandard based on these recommendations was to review such practices on a case-by-case baprobable outcome was that HIV-infected physicians would be forced to abandon surgical careerequired to explain risks to potential surgical patients.A review by Julie Gerberding of the CDC did not mention these recommendations regardingmanagement of HIV-infected health care workers (Ann Intern Med 1999;130:64), but did emphfollowing: Patients who have exposures analogous to what would be defined as a potentially hioccupational exposure in a health care worker should be managed by standard guidelines withto counseling, serologic testing, and antiretroviral therapy. This means that a patient exposed tfrom an HIV-infected surgeon, such as an accidental needle injury resulting in contamination ofsurgical field with the surgeons blood, needs counseling regarding the exposure and the optionantiretroviral treatment. One issue that is often overlooked is that anonymity is an ethical and lerequirement for the health care workers interacting with HIV-infected patients, but there are no
    • occupational exposure in a health care worker should be managed by standard guidelines with to counseling, serologic testing, and antiretroviral therapy. This means that a patient exposed t from an HIV-infected surgeon, such as an accidental needle injury resulting in contamination of surgical field with the surgeons blood, needs counseling regarding the exposure and the option antiretroviral treatment. One issue that is often overlooked is that anonymity is an ethical and le requirement for the health care workers interacting with HIV-infected patients, but there are no restrictions on the patient who is notified about a health care worker with HIV. Disclosure of a s serologic status may end his/her career. Top of Page | Next page -- Postexposure Prophylaxis for Sexual Contact or Needle SharinCopyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rightsreserved.* Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained inthis site because no single reference or service can take the place of medical training, education, and experience. Consumers arecautioned that this site is not intended to provide medical advice about any specific medical condition they may have or treatmentthey may need and they are encouraged to call or see their physician or other health care provider promptly with any health relatedquestions they may have.
    • Go to a Chapter Table of Contents Natural History and Classification Laboratory Tests Disease Prevention Antiretroviral Therapy Managem Opportunistic Infections Drugs: Guide to Information Systems Review CorrectionsIV. Antiretroviral TherapyRecommendations for Antiretroviral Therapy Goals of Therapy Terms and Concepts Antiretroviral Therapy for HIV Infected Patients Recommendations for Antiretroviral Therapy in Pregnancy Postexposure Prophylaxis for Health Care Workers Postexposure Prophylaxis for Sexual Contact or Needle SharingAntiretroviral Agents Nucleoside Analogs Non-nucleoside Reverse Transcriptase Inhibitors (NNRTI) Protease Inhibitors Class Adverse Reactions to Antiretroviral AgentsTables Table 4-16: Antiretroviral Drugs Approved by FDA for HIV Table 4-20: Drugs That Should Not be Used with Protease Inhibitors or NNRTIs* Table 4-21: Drug Interactions Requiring Dose Modifications or Cautious Use Table 4-22: Drug Interactions: Protease Inhibitors and Non-Nucleoside Reverse Transcriptase Inhibitors Effect of Drug on Levels (AUCs)/Dose Table 4-27: HIV-Related Drugs with Overlapping Toxicities Table 4-28: Dosing of Antiretroviral Agents in Renal and Hepatic Failure Table 4-29: Characteristics of Antiretrovirals During Dialysis I. Recommendations for Antiretroviral TherapyBased on the recommendations of the DHHS/Kaiser Family Foundation as of May 2001; (DHHS PClinical Practices for Treatment of HIV Infection Guidelines for Use of Antiretroviral Agents in HIV-Adults and Adolescents); available at http://www.hivatis.org. Print copies may be obtained from HIVTreatment Information Service, P.O. Box 6303, Rockville, MD 20849-6303; telephone: 800-448-04D. PEP for Sexual Contact or Needle Sharing
    • 1. CDC Recommendations (MMWR 1998;47[RR-17]) a. Conclusion: The PHS is unable to recommend for or against prophylaxis after nonoccup exposure due to the lack of data. b. If prophylaxis is attempted, the health care provider must: inform the patient about the lack of data make judicious use of antiretroviral agents (no specific regimen is recommended) address patients needs for risk reduction restrict use of PEP to high-risk exposures: unprotected receptive and or vaginal interc with a known HIV-infected source. c. Miscellaneous issues Cost: $800 (estimate for 28-day course of antiretroviral agents) Current practice guidelines: British Columbia Centre for Excellence in HIV/AIDS pu "A Guideline for Accidental Exposure to HIV," which recommends antiretroviral agents victims. The Center provides a "starter kit" with a 5-day supply of AZT and 3TC to em rooms. Registry: The CDC has established a new Nonoccupational HIV Postexposure Proph Registry that includes 6 forms and 17 pages. All information can be provided by teleph 877-448-1737, on the Web site (http://www.hivpepregistry.org), or by hard copy. Write Nonoccupational HIV PEP Registry, John Snow Inc., 44 Farnsworth St., Boston, MA 02210-1211; fax 877-448-7737. The provider incentive is a $10 gift certificate to a nati chain. Table 4-15: Risk of HIV Transmission With Single Exposure From an HIV-Infected So Exposure Probability/10,000 exposures* Needle sharing 67 Percutaneous (occupational exposure) 30 Receptive anal intercourse 10 to 30 Receptive vaginal intercourse 8 to 20 Insertive vaginal sex 3 to 9 Insertive anal sex 3 * (Am J Med 1999;106:324; Ann Intern Med 1996;125:497; J AIDS 1992;5:1116; N Engl J Med 1997;336:102. Recommendations of M. Katz and J. Gerberding, San Francisco Department of Public and UCSF (Ann Intern Med 1998;128:306; Am J Med 1999;106:323) a. Recommendations for PEP: Risk is high: unprotected receptive anal intercourse, unprotected receptive vaginal inte unprotected insertive vaginal intercourse; unprotected insertive anal intercourse or un receptive fellatio with ejaculation and Patients partner is known to have HIV infection or to be in a highrisk category (gay ma injection drug user, sex worker, etc.) and Exposure is an isolated event and patient has made a commitment to safer sex in the and The exposure occurred <72 hours of presentation for care b. Treatment regimens x 4 weeks Standard: Combivir (AZT 300 mg bid/3TC 150 mg bid) Alternative: d4T (40 mg bid) + ddI (400 mg qd) Protease inhibitor: Consider adding NFV (1250 mg bid with meals) or IDV (800 mg tid
    • The exposure occurred <72 hours of presentation for care b. Treatment regimens x 4 weeks Standard: Combivir (AZT 300 mg bid/3TC 150 mg bid) Alternative: d4T (40 mg bid) + ddI (400 mg qd) Protease inhibitor: Consider adding NFV (1250 mg bid with meals) or IDV (800 mg tid empty stomach) or IDV + RTV or LPV/RTV (400/100 mg bid) if source has either viral load >50,000 c/mL, advanced HIV disease or source has been treated with one or bot NRTIs c. Testing of exposed patient (pregnancy test if appropriate): HIV, HCV, HBV, gonorrhea, Chlamydia trachomatis; baseline tests for PEP-CBC, liver function tests, renal function te d. Cost: Estimated at $500 for the two-NRTI regimen and $1100 to $1200 for the PI-contain regimen. Medical care and laboratory testing add about $500 for a total of $1000 to $1700 e. Preliminary experience reported at ICAAC September 1998 by J. N. Martin (Abstrac Number treated: 202 Type of exposure: Sexual exposure - 91%, needle sharing - 0.5% Treatment: AZT/3TC - 82%, d4T/ddI - 11%, PI-containing regimen - 3% Number who discontinued regimen prior to 4 weeks - 8% 3. Vancouver General Hospital experience with sexual assault (Can Med Assoc J 2000;1 Number treated: 258 Number accepting 5-day starter pack: 29 Number completing 4-week course: 8 Top of Page | Next page -- Table 4-16: Antiretroviral Drugs Approved by FDA for HIVCopyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rightsreserved.* Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained inthis site because no single reference or service can take the place of medical training, education, and experience. Consumers arecautioned that this site is not intended to provide medical advice about any specific medical condition they may have or treatmentthey may need and they are encouraged to call or see their physician or other health care provider promptly with any health relatedquestions they may have.
    • Go to a Chapter Table of Contents Natural History and Classification Tests Disease Prevention Antiretroviral Therapy Management of Opp Infections Drugs: Guide to Information Systems Review HIV in CorrecIV. Antiretroviral Therapy Recommendations for Antiretroviral Therapy Goals of Therapy Terms and Concepts Antiretroviral Therapy for HIV Infected Patients Recommendations for Antiretroviral Therapy in Pregnancy Postexposure Prophylaxis for Health Care Workers Postexposure Prophylaxis for Sexual Contact or Needle Sharing Antiretroviral Agents Nucleoside Analogs Non-nucleoside Reverse Transcriptase Inhibitors (NNRTI) Protease Inhibitors Class Adverse Reactions to Antiretroviral Agents Tables Table 4-16: Antiretroviral Drugs Approved by FDA for HIV Table 4-20: Drugs That Should Not be Used with Protease Inhibitors or NNRTIs* Table 4-21: Drug Interactions Requiring Dose Modifications or Cautious Use Table 4-22: Drug Interactions: Protease Inhibitors and Non-Nucleoside Reverse Transcriptase InhibitorsEffect of Drug on Levels (AUCs)/Dose Table 4-27: HIV-Related Drugs with Overlapping Toxicities Table 4-28: Dosing of Antiretroviral Agents in Renal and Hepatic Failure Table 4-29: Characteristics of Antiretrovirals During Dialysis II. Antiretroviral Agents A. NUCLEOSIDE ANALOGS
    • Table 4-17: Nucleoside AnalogsDrug AZT, ZDV ddI ddC d4T 3TCTrade Name Retrovir Videx and Videx EC Hivid Zerit EpivirHow Supplied 0.375 & 0.75 15, 20, 30, and 40 mg tabs mg caps 100 and 300 mg tabs; 25, 50, 100, and 150 mg 1 mg/mL oral soln 150 mg tabs; 300 mg + 3TC buffered tabs; 150 mg with AZT 300 150 mg as Combivir; 100, 167, and 250 mg mg as Combivir; 10 300 mg + 3TC 150 mg powder packets; mg/mL oral solution; + ABC; 200 mg buffered tabs 150 mg with AZT 300 300 mg as Trizivir mg and ABC 300 mg as for 1-2x daily dosing; 10 mg/mL oral solution Trizivir 120, 200, 250, and 400 mg enteric coated cap (Videx EC); Pediatric powder with 4 g/240 mLDosing 300 mg bid 0.75 mg tid >60kg: 40mg bidRecommendations (or with 3TC as <60kg: 30mg bid Combivir 1 tab bid or Tablets or oral soln* 150 mg bid or with AZT with 3TC + ABC as >60kg: 200 mg bid or 400 as Combivir (1 tab bid) Trizivir 1 tab bid) mg qd (tabs) or 250 mg bid or with AZT + ABC as or 500 mg qd (powder); 400 Trizivir (1 tab bid) mg cap (Videx EC ) qd <60kg: 250 mg qd or 125 mg bid (tabs) or 167 mg bid or 250 mg qd (powder) or Videx EC 250 mg qdOral Bioavailability 60% 30% to 40% 85% 86% 86%Food Effect None; may be better Levels 55% None None None tolerated with food Videx - Take 1/2 hour before and 2 hours after meal; Videx EC - take 1 hour before and 2 hours after mealSerum Half-life 1.1 hours 1.6 hours 1.2 hours 1.0 hour 3 to 6 hoursIntracellular 3 hours 25 to 40 hours 3 hours 3.5 hours 12 hoursHalf-lifeCNS Penetration 60% 20% 20% 30% to 40% 10%(% serum levels)Elimination Metabolized to AZT Renal excretion - 50% Renal Renal excretion - Renal excretion Glucuronide (GAZT) excretion - 50% unchanged Renal excretion of 70% GAZTMajor Toxicity Bone marrow Peripheral Peripheral Minimal toxicityClass Toxicity suppression: anemia neuropathy neuropathy and/or neutropenia Pancreatitis Stomatitis Avoid Subjective complaints: Peripheral neuropathy combination with GI intolerance, GI intolerance - nausea, ddI in pregnancy headache, insomnia, diarrhea. Videx EC has fewer asthenia GI side effects Avoid combination with d4T in pregnancyDrug Interactions Ribavirin may reduce Methadone ddI levels None Methadone ddI None AZT activity 41%; consider ddI dose levels 27% No increase dose adjustment.* For adults, ddI pediatric oral solution can be mixed by the pharmacist with liquid antacids. See package insert for ins
    • * For adults, ddI pediatric oral solution can be mixed by the pharmacist with liquid antacids. See package insert for ins Lactic acidosis with hepatic steatosis is a rare but potentially life-threatening toxicity probably seen with all NRTIs, bu with d4T, ddI, and AZT. The combination of d4T + ddI should be avoided in pregnancy due to risk of lactic acidosis and hepatotoxicity (see Reactions).Top of Page | Next page -- Table 4-18: Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)Copyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rightsreserved.* Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained inthis site because no single reference or service can take the place of medical training, education, and experience. Consumers arecautioned that this site is not intended to provide medical advice about any specific medical condition they may have or treatmentthey may need and they are encouraged to call or see their physician or other health care provider promptly with any health relatedquestions they may have.
    • Go to a Chapter Table of Contents Natural History and Classification Tests Disease Prevention Antiretroviral Therapy Management of Opp Infections Drugs: Guide to Information Systems Review HIV in CorrecIV. Antiretroviral Therapy Recommendations for Antiretroviral Therapy Goals of Therapy Terms and Concepts Antiretroviral Therapy for HIV Infected Patients Recommendations for Antiretroviral Therapy in Pregnancy Postexposure Prophylaxis for Health Care Workers Postexposure Prophylaxis for Sexual Contact or Needle Sharing Antiretroviral Agents Nucleoside Analogs Non-nucleoside Reverse Transcriptase Inhibitors (NNRTI) Protease Inhibitors Class Adverse Reactions to Antiretroviral Agents Tables Table 4-16: Antiretroviral Drugs Approved by FDA for HIV Table 4-20: Drugs That Should Not be Used with Protease Inhibitors or NNRTIs* Table 4-21: Drug Interactions Requiring Dose Modifications or Cautious Use Table 4-22: Drug Interactions: Protease Inhibitors and Non-Nucleoside Reverse Transcriptase InhibitorsEffect of Drug on Levels (AUCs)/Dose Table 4-27: HIV-Related Drugs with Overlapping Toxicities Table 4-28: Dosing of Antiretroviral Agents in Renal and Hepatic Failure Table 4-29: Characteristics of Antiretrovirals During Dialysis II. Antiretroviral Agents B. NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS (NNRTIs)
    • Table 4-18: Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) Drug NVP DLV EFV Trade Name Viramune Rescriptor Sustiva Form 200 mg tabs; 50 mg/mL oral solution 100 mg and 200 mg tabs 50, 100, 200 mg caps Dosing 200 mg PO qd x 14 days, then 200 mg 400 mg PO tid 600 mg PO qd (in the evening) Recommendations PO bid Oral Bioavailability >90% 85% 42% Food Effect No effect No effect Absorption increased 50% with high-fat meal; avoid meal Serum Half-life 25 to 30 hours 5.8 hours 40 to 52 hours Elimination Metabolized by cytochrome P450 (3A4 Metabolized by cytochrome Metabolized by cytochrome P450 enzymes (3A4 mi inducer); 80% excreted in urine P450 (3A4 inducer); 51% inhibitor/inducer); 14% to 34% excreted in urine, (<1 (glucuronidated metabolites, <5% excreted in urine (<5% 16% to 61% in feces unchanged), 10% in feces unchanged), 44% in feces Major toxicity Rash (15% to 30%); discontinuation Rash (10% to 15%); CNS: dizziness, "disconnectedness," somnolence, Class Toxicity required in 7%; rare cases of discontinuation required in 4% abnormal dreams, confusion, amnesia, agitation, ha Stevens-Johnson syndrome Increased transaminase levels poor concentration - 40% to 50%, usually resolves w Hepatitis with hepatic necrosis weeks; take in evening; discontinuation of EFV for C 2.6% Rash (5% to 10%); discontinuation required in 1.7% of Stevens-Johnson syndrome Teratogenic in cynomalgus monkeys (see Table pregnancy and women should use adequate contrac methods. False-positive drug screening test for cannabinoids Top of Page | Next page -- Table 4-19: Protease InhibitorsCopyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rightsreserved.* Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained inthis site because no single reference or service can take the place of medical training, education, and experience. Consumers arecautioned that this site is not intended to provide medical advice about any specific medical condition they may have or treatmentthey may need and they are encouraged to call or see their physician or other health care provider promptly with any health relatedquestions they may have.
    • Go to a Chapter Table of Contents Natural History and Classification Tests Disease Prevention Antiretroviral Therapy Management of Opp Infections Drugs: Guide to Information Systems Review HIV in CorrecIV. Antiretroviral Therapy Recommendations for Antiretroviral Therapy Goals of Therapy Terms and Concepts Antiretroviral Therapy for HIV Infected Patients Recommendations for Antiretroviral Therapy in Pregnancy Postexposure Prophylaxis for Health Care Workers Postexposure Prophylaxis for Sexual Contact or Needle Sharing Antiretroviral Agents Nucleoside Analogs Non-nucleoside Reverse Transcriptase Inhibitors (NNRTI) Protease Inhibitors Class Adverse Reactions to Antiretroviral Agents Tables Table 4-16: Antiretroviral Drugs Approved by FDA for HIV Table 4-20: Drugs That Should Not be Used with Protease Inhibitors or NNRTIs* Table 4-21: Drug Interactions Requiring Dose Modifications or Cautious Use Table 4-22: Drug Interactions: Protease Inhibitors and Non-Nucleoside Reverse Transcriptase InhibitorsEffect of Drug on Levels (AUCs)/Dose Table 4-27: HIV-Related Drugs with Overlapping Toxicities Table 4-28: Dosing of Antiretroviral Agents in Renal and Hepatic Failure Table 4-29: Characteristics of Antiretrovirals During Dialysis
    • II. Antiretroviral Agents C. PROTEASE INHIBITORSTable 4-19: Protease InhibitorsDrug IDV RTV SQVTrade Name Crixivan Norvir Invirase FortovaseSupplier Merck Abbott Roche RocheForm 200, 400, 333 mg caps 100 mg caps 200 mg caps 200 mg caps (soft-gel caps) 600 mg/7.5 mL PO (hard-gel caps) solutionUsual Dose 800 mg q8h 600 mg bid* 400 mg bid with 1200 mg tid Separate buffered ddI dose Separate buffered RTV (only use of by 1 hour ddI dose by 2 Invirase) hoursFood effect Levels decreased 77%; Levels increased No food effect Levels increase 6x; take with take 1 hour before or 2 15%; take with when taken with large meal unless taken with RTV hours after meals; may take food if possible to RTV with low-fat snack or skim imporve tolerability milkBioavailability 65% (on empty stomach) Not determined 4% Not determined (estimated to be 13x higher than Invirase)Storage Room temperature Soft-gel cap and Room temperature Room temperature or refrigerate liquid formulation - room temperatureSerum Half-life 1.5 to 2 hours 3 to 5 hours 1 to 2 hours 1 to 2 hoursCNS Penetration Moderate Poor Poor PoorElimination Biliary metabolism Biliary metabolism Biliary metabolism Biliary metabolism P450 cytochrome, CYP P450 cytochrome, P450 cytochrome, P450 cytochrome, 3A4 inhibitor 3A4 inhibitor 3A4>2D6; most 3A4 inhibitor potent 3A4 inhibitorSide Effects GI intolerance (10% GI intolerance GI intolerance (20% to (10% to 20%) to 15%) GI intolerance 30%) Misc. - headache, Nephrolithiasis or (20% to 40%) - transaminase Misc. - headache, nephrotoxicity (10% nausea, vomiting, levels increase increased to 20%) take >1.5 diarrhea; Class Adverse transaminase levels, Circumoral and Reactions L/day; Misc. - extremities (10%) hypoglycemia in diabetes headache, blurred Taste perversion Class Adverse Reactions vision, (10%) thrombocytopenia, Lab - increased triglyceride levels in paronychia, hepatitis, 60% and increased asthenia, dizziness, transaminase rash, metallic taste, levels in 10% to ITP, alopecia, dry 15%, increased skin, chapped lips CPK and uric acid Misc. - asthenia, Lab - increase hepatitis, alcohol indirect bilirubinemia content of oral (inconsequential) solution contains Class Adverse ETOH, possible disulfiram reaction Reactions Class Adverse Reactions
    • indirect bilirubinemia content of oral (inconsequential) solution contains Class Adverse ETOH, possible disulfiram reaction Reactions Class Adverse Reactions* Dose escalation for RTV: days 1 and 2: 300 mg bid; days 3 to 5: 400 mg bid; days 6 to 13: 500 mg bid; day 14: 600 mg bid. Combination treatment rePO bid) plus RTV (400 mg PO bid). Top of Page | Next page -- Table 4-20: Drugs That Should not be Used with Protease ICopyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rightsreserved.* Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained inthis site because no single reference or service can take the place of medical training, education, and experience. Consumers arecautioned that this site is not intended to provide medical advice about any specific medical condition they may have or treatmentthey may need and they are encouraged to call or see their physician or other health care provider promptly with any health relatedquestions they may have.
    • Go to a Chapter Table of Contents Natural History and Classification Tests Disease Prevention Antiretroviral Therapy Management of Opp Infections Drugs: Guide to Information Systems Review HIV in CorrecIV. Antiretroviral Therapy Recommendations for Antiretroviral Therapy Goals of Therapy Terms and Concepts Antiretroviral Therapy for HIV Infected Patients Recommendations for Antiretroviral Therapy in Pregnancy Postexposure Prophylaxis for Health Care Workers Postexposure Prophylaxis for Sexual Contact or Needle Sharing Antiretroviral Agents Nucleoside Analogs Non-nucleoside Reverse Transcriptase Inhibitors (NNRTI) Protease Inhibitors Class Adverse Reactions to Antiretroviral Agents Tables Table 4-16: Antiretroviral Drugs Approved by FDA for HIV Table 4-20: Drugs That Should Not be Used with Protease Inhibitors or NNRTIs* Table 4-21: Drug Interactions Requiring Dose Modifications or Cautious Use Table 4-22: Drug Interactions: Protease Inhibitors and Non-Nucleoside Reverse Transcriptase InhibitorsEffect of Drug on Levels (AUCs)/Dose Table 4-27: HIV-Related Drugs with Overlapping Toxicities Table 4-28: Dosing of Antiretroviral Agents in Renal and Hepatic Failure Table 4-29: Characteristics of Antiretrovirals During Dialysis II. Antiretroviral Agents
    • CLASS ADVERSE DRUG REACTIONS (ADRs) TO ANTIRETROVIRAL AGENTS(DHHS Guidelines Supplement November 1998, with additions by author)Several class-related adverse events have been recognized with antiretroviral drugs during the posperiod. For NRTIs, lactic acidosis with hepatomegaly and hepatic steatosis has been reported. Forof hyperglycemia/diabetes mellitus, increased bleeding episodes in patients with hemophilia, andlipodystrophy with and without serum lipid abnormalities have been received. Because these eventsidentified based on spontaneous reports and other uncontrolled data, the actual incidence of theseand the causal association with these drugs have not been definitively established. Controlled and/opopulation-based epidemiologic studies evaluating these potential class adverse events are warranNUCLEOSIDE ANALOGSLactic Acidosis/Hepatic SteatosisLactic acidosis and severe hepatomegaly with steatosis during use of NRTIs appear to occur at a lofrequency, but with a high case fatality risk (Lancet 1994;343:1494). One retrospective database anshowed an incidence of 1.3 per 1000 patient-years among patients who received NRTIs. The incideelevations in serum lactate may be as high as 5% to 10% with more aggressive diagnostic evaluatioon serum lactate levels (39th ICAAC, San Francisco, Calif., September 1999, Abstract 1285; 7th CRFrancisco, Calif., February 2000, Abstract S21, 42, 55, 56, and 57). Patients typically present with fnausea, vomiting, abdominal pain, weight loss, and dyspnea . Evaluation reveals elevated serum laor without metabolic acidosis, and may show elevated CPK, ALT, and/or LDH, increased anion gapbicarbonate. Abdominal CT scan or liver biopsy often shows steatotosis (Ann Intern Med 2000;13:1initial clinical manifestations of lactic acidosis are variable and may include nonspecific GI symptomdramatic elevation of hepatic enzymes, and in some cases dyspnea. Fatalities have been reported dintensive supportive treatment; in other cases, the adverse event has resolved after discontinuationAll NRTIs have been implicated, although some studies suggest higher rates with d4T or ddI/hydrox(HU). The frequency with 3TC and with ABC appears to be low, but data are inconsistent. It is possother clinical expressions of mitochondrial toxicity include myopathy, cardiomyopathy, neuropathy,pancreatitis, asthenia, and/or lipoatrophy (7th CROI, San Francisco, Calif., February 2000, Abstractmost important therapeutic intervention is discontinuation of NRTIs. Lactic acidemia resolves slowlyover a period of 3 to 6 months. The safety of substituting alternative drugs in the NRTI class is not kpreliminary data suggest that substitution of regimens that dont contain 3TC or ABC in place of d4TddI may be successful. There is limited experience with antiretroviral regimens that dont contain nubut the largest (and best) experience has been with IDV + EFV + SQV + RTV; also attractive is LPVEFV. One report suggests that lactic acidosis may respond to 50 mg riboflavin (Lancet 1998;252:29suggested treatments (without established merit) are coenzymes (thiamine), antioxidants (compounelectron acceptors (vitamin C), and L-carnitine (Lancet 2000;356:1424). Other toxicities that may beto mitochondrial toxicity are presented in the table below:4-23: Known and Possible NRTI Complications Possibly Ascribed to Mitochondrial Toxicity(Adapted from Carr A, Cooper DA. Lancet 2000;356:1423)Drug Organ Rate Features Lab RxAZT Skeletal 17% Fatigue, myalgias, CPK Discontinuation muscle proximal muscle wastingAZT Cardiac Rare Dilated cardiomyopathy Echocardiogram Discontinuation muscleAZT Marrow 5% to 10% Anemia and/or CBC G-CSF neutropenia Erythropoietin (EPO), discontinuation
    • AZT Marrow 5% to 10% Anemia and/or CBC G-CSF neutropenia Erythropoietin (EPO), discontinuationd4T Peripheral 10% to Painful peripheral Axonal TricyclicddI nerve 30% neuropathy with degeneration on antidepressants,ddC paresthesias, reduced biopsy gabapentin, reflexes (ankle jerks) lamotrigine, discontinuationddI Pancreas 1% to 6% Abdominal pain amylase Discontinuation (d4T, 3TC)d4T Tissue 50% Fat loss - face, None Discontinuation (may (AZT, ddI) (lipoatrophy) extremities, buttocks be irreversible)NNRTIsRashRash is a relatively common toxicity encountered during use of NNRTIs. A significant minority of theare severe, and potentially fatal cases of Stevens-Johnson syndrome have been reported. The medof onset is at 1 to 3 weeks. The frequency is 15% to 20% with NVP and DLV, and 8% to 10% with Eseverity sufficient to require to require discontinuation is 7% with NVP and 2% with EFV.PIsLipodystrophy, hyperlipidemia, and insulin resistance have been associated with PI use with variablfrequency. These changes may occur together or as isolated observations. The etiologic role of PIsconsidered established by some, and the long-term consequences are generally unclear. Recommefor monitoring and intervention are also unclear at the present time.HyperglycemiaInsulin resistance decreased glucose tolerance, hyperglycemia, new-nset diabetes mellitus, diabeticketoacidosis, and exacerbation of existing diabetes mellitus in patients receiving PIs have been rep(Lancet 1997;350:317; Ann Intern Med 1997;127:947; Ann Intern Med 1997;127:948). Among thesesymptom onset occurred a median of 63 days (range 2 to 390 days) following initiation of PI therapyHyperglycemia resolved in some patients who discontinued PI therapy; however, the reversibility ofevents is currently unknown due to limited data. Some patients continued PI therapy and initiated trwith oral hypoglycemic agents or insulin. Clinicians are advised to monitor HIV-infected patients withpreexisting diabetes closely when PIs are prescribed, and to be aware of the risk for drug-related nediabetes in patients without a history of diabetes. Patients should be advised about the warning signhyperglycemia (ie, polydipsia, polyphagia, and polyuria) when these medications are prescribed. Soauthorities recommend routine fasting blood glucose measurements at 3- to 4-month intervals durintreatment. Routine use of glucose tolerance tests to detect this complication is not recommended. Tno data to aid in the decision to continue or discontinue drug therapy in cases of new-onset or worsdiabetes; however, most experts would recommend continuation of HAART, but not necessarily witthe absence of severe, life-threatening diabetes.LipodystrophyChanges in body fat distribution, sometimes referred to as "lipodystrophy syndrome" or "fat redistribsyndrome" have been observed in 13% to 84% of patients taking protease inhibitors (AIDS 1999;13The frequency with which this change is noted by the patient and confirmed by the care provider witPI-based HAART and an 18-month follow-up in one large study was 17%. Clinical findings include c
    • LipodystrophyChanges in body fat distribution, sometimes referred to as "lipodystrophy syndrome" or "fat redistribsyndrome" have been observed in 13% to 84% of patients taking protease inhibitors (AIDS 1999;13The frequency with which this change is noted by the patient and confirmed by the care provider witPI-based HAART and an 18-month follow-up in one large study was 17%. Clinical findings include cobesity and peripheral fat wasting. The changes may include visceral fat accumulation, dorsocervicaccumulation ("buffalo hump"), loss of buttock fat and subcutaneous fat in the extremities with venoprominence, facial thinning, breast enlargement, and lipomatosis (Lancet 1998;351:871; Lancet1998;351:867; Lancet 1997;350:1596; Lancet 1998;352:1881; J AIDS 1999;21:107). Some patientsfat accumulation and fat atrophy may have a cushingoid appearance despite the absence of measuabnormalities in adrenal function. It is unclear whether the various clinical manifestations represententities with different etiologies, or whether they occur as a result of a single pathologic process. Simfindings have also been reported in HIV-infected patients not receiving PIs (Lancet 1998;351:867);the number of reports has increased concomitantly with the widespread use of PI-containing antiretrregimens. Some experts believe that fat atrophy is due to NRTI-associated mitochondrial toxicity, esas a result of d4T, ddI, and AZT while fat accumulation is due to PIs, and is often associated with inresistance and hyperlipidemia. A review of published reports in 1999 showed the frequencies of varchanges as follows: buffalo hump (2% to 5%), breast enlargement (1% to 13%), abdominal paunch21%), face atrophy (1% to 22%), and extremity wasting (8% to 13%) (AIDS 1999;13:2493). There adata on management recommendations.HyperlipidemiaChanges in triglycerides and/or cholesterol have occurred with or without the clinical findings of fatredistribution. In clinical studies, all PIs have been implicated, but RTV has been shown to producesubstantial increases in triglycerides and cholesterol. Although the long-term consequences of fatredistribution are unknown, substantial increases in triglycerides or cholesterol are of concern becaupossible association with cardiovascular events and pancreatitis. In this regard, case reports have adescribing premature coronary artery disease, cerebrovascular disease, and cholelithiasis in patientreceiving PI therapy. Some authorities recommend monitoring of serum levels of cholesterol and trigat 3- to 4-month intervals during PI therapy. Assessment should include evaluation for independentcardiovascular disease (ie, family history, medical history, smoking, diet, weight, etc.) and the magnlipid changes. Intervention is often recommended for triglyceride levels >750 to 1000 mg/dL and/orcholesterol levels >130 mg/dL (in individuals without known coronary disease or with two or more corisk factors) or >160 mg/dL (in individuals without known coronary disease and with fewer than tworisk factors). The effectiveness of dietary modification and lipid-lowering drugs such as gemfibrozil ais not clear. Some patients have had resolution of serum lipid abnormalities with discontinuation of Phowever, this decision requires a risk-benefit analysis.Management of dyslipidemia (Recommendations of the ACTG, Dubé et al. Clin Infect Dis 2000;31:1 Monitoring: Fasting (8 to 12 hours) cholesterol, HDL cholesterol, and triglycerides at baseline and at 3 to 6 months. Frequency of monitoring thereafter depends on results and risk profile. N that RTV may cause significant increase in cholesterol levels within 2 weeks. Risk: Risk of premature cardiovascular events with hyperlipidemia with PI therapy is not know but is suspected (Lancet 1998;351:1328; Lancet 1998;351:1958, Lancet 1998;351:1959). Magnitude: Mean increase in cholesterol with PI therapy is reported at 32 mg/dL at 3.4 month with LDL increase of 18 mg/dL. Switch: Data are incomplete, but one study shows a favorable response to PI substitution wit NVP (AIDS 1999;14:805), EFV (Clin Infect Dis 2000;31:1266), or ABC (7th CROI, San Franci Calif., February 2000, Abstract 51). Recommendations: National Cholesterol Education Program Treatment (NCEPT) (Circulatio
    • Switch: Data are incomplete, but one study shows a favorable response to PI substitution wit NVP (AIDS 1999;14:805), EFV (Clin Infect Dis 2000;31:1266), or ABC (7th CROI, San Franci Calif., February 2000, Abstract 51). Recommendations: National Cholesterol Education Program Treatment (NCEPT) (Circulatio 1994;89:1329) based primarily on LDL levels and risks, with particular emphasis on patients w diabetes or prior cardiovascular disease (Ann Intern Med 2000;133:549). Table 4-24: NCEPT Guidelines Based on LDL Cholesterol (JAMA 2001;285:2486) Pt. status Diet change Drug Rx Target LDL No coronary heart disease (CHD) <2 risk* >160 >190 <160 >2 risk >130 130-160* <130 Coronary heart disease, diabetes or >100 >130 <100 high risk profile * Risks: Age - men >45, women >55 or premature menopause without estrogen replacement; first degree relative with CHD in male <55 or female <65, hypertension, diabetes, current smoking LDL is calculated from triglycerides and is unreliable if triglycerides are >400 mg/dL. Diet therapy is recommended if triglycerides are >400, cholesterol is >240 mg/dL, or HDL cholesterol is <35. Risk profile defined by age, cholesterol, HDL, and systolic blood pressure. Triglycerides: Drug therapy if triglyceride levels are >500 mg/dL. Usual treatment is a fibrate (genfibrozil 600 mg bid or fenofibrate 201 mg/day or nicotonic acid).Drugs Statins: Concern is that many are metabolized by cytochrome P450 pathways and cases of rhabdomyolysis have been reported with simvastatin (40th ICAAC, Toronto, Canada, Septemb Abstract 1297). Cytochrome P450 3A4/5 isozymes are responsible for metabolism of most sta most PIS and NNRTIs. Table 4-25: Concurrent Use of Statins and PIs Agent Metabolism PI/NNRTI Interactions Lovastatin CYP3A4 Avoid PIs, avoid DLV Simvastatin (Nephron 1993;65:410); No data on EFV and NVP - recommend avoidin (South Med J 1998;91:202) concurrent use Fluvastatin CYP2C9 Interaction with NFV; concurrent use not studie (Int J Clin Pharmacol Ther 1995;33:246) SQV, RTV, APV, LPV/RTV, EFV, or NVP Cerivastatin Limited data Concurrent use not studied with IDV, SQV, RTV NFV, LPV/RTV, EFV, or NVP Atorvastatin* CYP3A4 Concurrent use okay with IDV, SQV, RTV, APV atorvastatin 6x with LPV/RTV Pravastatin* No cytochrome P450 interactions Concurrent use okay with IDV, SQV, RTV, APV (Clin Pharmacol Ther 1998;63:332) *Preferred by ACTG committee for concurrent use with PIs and NNRTIs ( Clin Infect Dis 200;31:1216). Table 4-26:Treatment of Hyperlipidemia Lipid problem Preferred Alternative Comment Isolated high LDL Statin* Fibrate Start low doses and titrate upwards. With P for myopathy.
    • Isolated high LDL Statin* Fibrate Start low doses and titrate upwards. With P for myopathy. High cholesterol and Statin or Start one and add Combination may increase risk of myopathy triglycerides fibrate other Isolated high triglycerides Fibrate Statin Combination may increase risk of myopathy *Statin: Pravastatin 20 mg/day or atorvastatin 10 mg/day Gemfibrozil 600 mg bid >30 minutes before meal or micronized fenofibrate 200 mg qdIncreased Bleeding Episodes in Patients With HemophiliaIncreased spontaneous bleeding episodes in patients with hemophilia A and B have been observeduse of PIs. Most of the reported episodes involved joints and soft tissues; however, more serious blepisodes including intracranial and GI bleeding, have been reported. The bleeding episodes occurremedian of 22 days after initiation of PI therapy. Some patients received additional coagulation factocontinuing PI therapy.Avascular necrosisAvascular necrosis is another possible late complication that may be due to HAART. There have bereported cases of osteonecrosis in patients with HIV (Clin Infect Dis 2000;31:1488). Reported ratesto 1.3%. The most common site is the femoral head; many patients have other risk factors includingabuse, hyperlipidemia, corticosteroid use, and hypercoagulability. Bone density studies using dual ex-ray aborptiometry (DEXA)-scanning show that osteopenia and osteoporosis are relatively commonthere is no clear association with PIs or with lipodystrophy (AIDS 2000;14:F63).HEPATOTOXICITYAll antiretroviral drugs have been implicated as causing hepatotoxicity. Lactic acidosis with hepaticoccurs with virtually all nucleosides (primarily d4T, ddI, and AZT); PIs (especially RTV) have been imin hepatitis, and hepatitis has also been seen with NNRTIs, particularly NVP (J Infect Dis 1998;177AIDS 1998;12:1722; Lancet 1997;349:924). Hepatotoxicity has also been seen in patients given anagents in the presence of HCV- or HBV-associated liver disease; it is often not clear whether this readverse reaction to the antiretroviral agent or an expression of immune reconstitution with enhanceactivity against the hepatitis virus (AIDS 1998;12:116; AIDS 1998;12:2289; Clin Infect Dis 1998;27:Despite these reports, a large review of patients with HIV co-infected with HCV who were followedprospectively showed no significant increase in hepatotoxicity compared with those without chronicno irreversible hepatotoxic effects were observed (JAMA 2000;283:74). It should be noted that therecommendation for 3TC is substantially lower for the treatment of HBV than that for HIV, so that Hresistance would be anticipated in the event of use of the standard HBV doses in the absence of coHIV suppression. Due to the excellent safety profile of 3TC, the usual recommendation is the doseantiretroviral activity (150 mg bid). Hepatotoxicity of most PIs appears to be increased approximatelin patients with HCV or HBV co-infection, but severe toxicity is rare. Of the currently available antiredrugs, the most hepatotoxic appears to be NVP followed by full-dose RTV (JAMA 2000;283:74); nethese agents appears to be more hepatotoxic in patients with chronic hepatitis. Therefore, antiretrovtherapy should generally not be avoided, and specific agents should not be avoided in patients withco-infection. Nevertheless, these patients should have careful monitoring of liver enzymes during thMonitoring of transaminase levels is recommended for all patients receiving NVP, regardless of whehave underlying liver disease. Patients with overt liver failure should have consideration of dose redAZT, all PIs, and all NNRTIs.
    • Top of Page | Next page -- Table 4-27: HIV-Related Drug with Overlapping ToxicitiesCopyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rightsreserved.* Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained inthis site because no single reference or service can take the place of medical training, education, and experience. Consumers arecautioned that this site is not intended to provide medical advice about any specific medical condition they may have or treatmentthey may need and they are encouraged to call or see their physician or other health care provider promptly with any health relatedquestions they may have.
    • Go to a Chapter Table of Contents Natural History and Classification Tests Disease Prevention Antiretroviral Therapy Management of Opp Infections Drugs: Guide to Information Systems Review HIV in CorrecIV. Antiretroviral Therapy Recommendations for Antiretroviral Therapy Goals of Therapy Terms and Concepts Antiretroviral Therapy for HIV Infected Patients Recommendations for Antiretroviral Therapy in Pregnancy Postexposure Prophylaxis for Health Care Workers Postexposure Prophylaxis for Sexual Contact or Needle Sharing Antiretroviral Agents Nucleoside Analogs Non-nucleoside Reverse Transcriptase Inhibitors (NNRTI) Protease Inhibitors Class Adverse Reactions to Antiretroviral Agents Tables Table 4-16: Antiretroviral Drugs Approved by FDA for HIV Table 4-20: Drugs That Should Not be Used with Protease Inhibitors or NNRTIs* Table 4-21: Drug Interactions Requiring Dose Modifications or Cautious Use Table 4-22: Drug Interactions: Protease Inhibitors and Non-Nucleoside Reverse Transcriptase InhibitorsEffect of Drug on Levels (AUCs)/Dose Table 4-27: HIV-Related Drugs with Overlapping Toxicities Table 4-28: Dosing of Antiretroviral Agents in Renal and Hepatic Failure Table 4-29: Characteristics of Antiretrovirals During Dialysis II. Antiretroviral Agents
    • Table 4-16: Antiretroviral Drugs Approved by FDA for HIV Generic Name Brand Name Manufacturer FDA Approval D (abbreviation) Zidovudine (AZT, ZDV) Retrovir GlaxoSmithKline March 1987 Didanosine (ddI) Videx Bristol Myers-Squibb October 1991 Zalcitabine (ddC) Hivid Hoffman-La Roche June 1992 Stavudine (d4T) Zerit Bristol Myers-Squibb June 1994 Lamivudine (3TC) Epivir GlaxoSmithKline November 1995 Saquinavir (SQV, hgc) Invirase Hoffman-La Roche December 1995 Ritonavir (RTV) Norvir Abbott Laboratories March 1996 Indinavir (IDV) Crixivan Merck & Co., Inc. March 1996 Nevirapine (NVP) Viramune Boehringer Ingelheim June 1996 Nelfinavir (NFV) Viracept Agouron Pharmaceuticals March 1997 Delavirdine (DLV) Rescriptor Pharmacia & Upjohn April 1997 Zidovudine/Lamivudine (AZT/3TC) Combivir GlaxoSmithKline September 1997 Saquinavir (SQV, sgc) Fortovase Hoffman-La Roche November 1997 Efavirenz (EFV) Sustiva DuPont Pharmaceuticals September 1998 Abacavir (ABC) Ziagen GlaxoSmithKline February 1999 Amprenavir (APV) Agenerase GlaxoSmithKline April 1999 Lopinavir/Ritonavir (LPV/RTV) Kaletra Abbott Laboratories September 2000 Top of Page | Next page -- Table 4-17: Nucleoside AnalogsCopyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rightsreserved.* Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained inthis site because no single reference or service can take the place of medical training, education, and experience. Consumers arecautioned that this site is not intended to provide medical advice about any specific medical condition they may have or treatmentthey may need and they are encouraged to call or see their physician or other health care provider promptly with any health relatedquestions they may have.
    • Go to a Chapter Table of Contents Natural History and Classification Tests Disease Prevention Antiretroviral Therapy Management of Opp Infections Drugs: Guide to Information Systems Review HIV in CorrecIV. Antiretroviral Therapy Recommendations for Antiretroviral Therapy Goals of Therapy Terms and Concepts Antiretroviral Therapy for HIV Infected Patients Recommendations for Antiretroviral Therapy in Pregnancy Postexposure Prophylaxis for Health Care Workers Postexposure Prophylaxis for Sexual Contact or Needle Sharing Antiretroviral Agents Nucleoside Analogs Non-nucleoside Reverse Transcriptase Inhibitors (NNRTI) Protease Inhibitors Class Adverse Reactions to Antiretroviral Agents Tables Table 4-16: Antiretroviral Drugs Approved by FDA for HIV Table 4-20: Drugs That Should Not be Used with Protease Inhibitors or NNRTIs* Table 4-21: Drug Interactions Requiring Dose Modifications or Cautious Use Table 4-22: Drug Interactions: Protease Inhibitors and Non-Nucleoside Reverse Transcriptase InhibitorsEffect of Drug on Levels (AUCs)/Dose Table 4-27: HIV-Related Drugs with Overlapping Toxicities Table 4-28: Dosing of Antiretroviral Agents in Renal and Hepatic Failure Table 4-29: Characteristics of Antiretrovirals During Dialysis II. Antiretroviral Agents
    • Table 4-20: Drugs That Should Not Be Used With Protease Inhibitors or NNRTIs* Drug Category IDV RTV SQV NFV DLV EFV APV Cardiac None Amiodarone, None None None None None encainide, flecainide, propafenone, quinidine, bepridil Lipid-lowering Simvastatin, Simvastatin, Simvastatin, Simvastatin, Simvastatin, None Simvastatin, agents lovastatin lovastatin lovastatin lovastatin lovastatin lovastatin Antimycobacterial RIF RIF (?) RIF, RIF RIF, RBT None RIF RBT Ca ++ channel None Bepridil None None None None Bepridil blocker Antihistamine Astemizole, Astemizole, Astemizole, Astemizole, Astemizole, Astemizole, Astemizole, terfenadine terfenadine terfenadine terfenadine terfenadine terfenadine terfenadine GI Cisapride Cisapride Cisapride Cisapride Cisapride, H2 Cisapride Cisapride blockers, proton pump inhibitors Neuroleptic None Clozapine, None None None None None pimezide Psychotropic Midazolam, Midazolam, Midazolam, Midazolam, Midazolam, Midazolam, Midazolam, triazolam triazolam triazolam triazolam triazolam triazolam triazolam Ergot alkaloid Dihydro- Dihydro- Dihydro- Dihydro- Dihydro- Dihydro- Dihydro- (vasoconstrictor) ergotamine, ergotamine, ergotamine, ergotamine, ergotamine, ergotamine, ergotamine, ergotamine ergotamine ergotamine ergotamine ergotamine ergotamine ergotamine (various forms) (various forms) (various forms) (various forms) (various forms) (various (various forms) forms) Herbs St. Johns wort St. Johns wort St. Johns wort St. Johns wort St. Johns wort St. Johns wort St. Johns wort *NVP: see nevirapine. Alternatives: RBT (MAC)--clarithromycin, EMB, azithromycin; Antihistamine--loratadine, fexofenadine, cetirizine; Psychotrophic-temazepam, lorazep Lipid-lowering--atorvastatin, pravastatin, fluvastatin, cerivastatin. Top of Page | Next page -- Table 4-21: Drug Interactions Requiring Dose Modifications or CautiCopyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rightsreserved.* Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained inthis site because no single reference or service can take the place of medical training, education, and experience. Consumers arecautioned that this site is not intended to provide medical advice about any specific medical condition they may have or treatmentthey may need and they are encouraged to call or see their physician or other health care provider promptly with any health relatedquestions they may have.
    • Go to a Chapter Table of Contents Natural History and Classification Tests Disease Prevention Antiretroviral Therapy Management of Opp Infections Drugs: Guide to Information Systems Review HIV in CorrecIV. Antiretroviral Therapy Recommendations for Antiretroviral Therapy Goals of Therapy Terms and Concepts Antiretroviral Therapy for HIV Infected Patients Recommendations for Antiretroviral Therapy in Pregnancy Postexposure Prophylaxis for Health Care Workers Postexposure Prophylaxis for Sexual Contact or Needle Sharing Antiretroviral Agents Nucleoside Analogs Non-nucleoside Reverse Transcriptase Inhibitors (NNRTI) Protease Inhibitors Class Adverse Reactions to Antiretroviral Agents Tables Table 4-16: Antiretroviral Drugs Approved by FDA for HIV Table 4-20: Drugs That Should Not be Used with Protease Inhibitors or NNRTIs* Table 4-21: Drug Interactions Requiring Dose Modifications or Cautious Use Table 4-22: Drug Interactions: Protease Inhibitors and Non-Nucleoside Reverse Transcriptase InhibitorsEffect of Drug on Levels (AUCs)/Dose Table 4-27: HIV-Related Drugs with Overlapping Toxicities Table 4-28: Dosing of Antiretroviral Agents in Renal and Hepatic Failure Table 4-29: Characteristics of Antiretrovirals During Dialysis II. Antiretroviral Agents
    • Table 4-21: Drug Interactions Requiring Dose Modifications or Cautious UseDrugs Affected IDV RTV SQV*Antifungals Ketoconazole Levels: IDV 68% Levels: ketoconazole 3x Levels: SQV 3x Dose: IDV 600 mg tid Dose: use with caution; do not Dose: Standard exceed 200 mg/dayAntimycobacterials Rifampin Levels: IDV 89% Levels: RTV 35% Levels: SQV 84% Contraindicated May increase hepatotoxicity (?) Contraindicated unless using RT RIF 600 mg qd or 2x to 3x/week Rifabutin Levels: IDV 32% Levels: SQV 40% Levels: RBT 4x Not recommended RBT 2x Dose: RBT to 150 mg qod Dose: RBT to 150 mg qd or 300 mg 2x to 3x/week; or dose 3x/week IDV 1000 mg tid RTV - standard dose Clarithromycin Levels: Clarithromycin 53% Levels: Clarithromycin 45% No dose adjustment Levels: Clarithromycin 77% SQV 177% Dose: Adjust for renal No dose adjustment; with RTV + insufficiency clarithromycin 150 mg 2x tp 3x/wOral Levels: ethinyl estradiol 40% No data Levels: Norethindrone 26%Contraceptives Use alternative method Ethinylestradiol 24% No dose adjustmentAnticonvulsants Unknown but may decrease IDV levels substantially. Use Unknown Unknown, but may decrease SQ Phenobarbitol alternative antiretroviral therapy or RTV + IDV Use with caution substantially Phenytoin CarbamazepineMethadone No change in methadone levels Methadone 37%, No data May require dose increaseMiscellaneous Grapefruit juice Grapefruit juice increases SQV Desipramine 145%, reduce IDV levels by 26% Dexamethasone decreases SQV dose Sildenafil: Do not exceed 25 mg/48 hours Sildenafil: Do not exceed 25 mg Theophylline 47%, monitor theophylline levels Many possible interactions (see product insert) Sildenafil: Do not exceed 25 mg/48 hours*Some drug interaction studies were conducted with Invirase. Results may not necessarily apply to use with FTV.Table 4-21: Drug Interactions Requiring Dose Modifications or Cautious Use (Continued)Drugs Affected NFV APV LPV/RTVAntifungals Ketoconazole No dose adjustment necessary Levels: Ketoconazole 44% APV 31%; combination under Levels ketoconazole 3x investigation LPV 13% Dose: ?Anti-Mycobacterials Rifampin Levels: NFV 82% Levels: APV 82% Levels LPV 75% Contraindicated Contraindicated Avoid Rifabutin Levels: NFV 32% Levels: APV 15% Levels: LPV 17%
    • Rifabutin Levels: NFV 32% Levels: APV 15% Levels: LPV 17% RBT 2x RBT 193% RBT: 3x, RBT dose t Dose: RBT to 150 mg qd Dose: RBT to 150 mg qod, APV 150 mg qod NFV 1000 mg tid dose-standard LPV/RTV - standard Clarithromycin No data No data Levels: APV 18% Clarithromycin no change Dose: usualOral Contraceptives Not studied Levels: Ethinylestradiol Levels: Norethindrone 18%, Use alternative method ethinylestradiol 47% use alternative method Use alternative methodAnticonvulsants Unknown, but may decrease NFV Unknown, but may decrease APV levels Unknown Phenobarbitol levels substantially substantially Monitor anticonvulsant leve Phenytoin Monitor anticonvulsant level CarbamazepineMethadone NFV decreases methadone No data Methadone 53% significantly but has minimal Titrate methadone dose effect on maintenance dose. MonitorMiscellaneous Sildenafil: Do not exceed 25 mg/48 Sildenafil: do not exceed 2 ABC: APV 30% hours Sildenafil: Do not exceed 25 mg/48 hours mg/48 hoursTable 4-21: Drug Interactions Requiring Dose Modifications or Cautious UseDrugs Affected NVP DLV EFVAntifungals Ketoconazole Levels: Ketoconazole 63% Not studied Not studied NVP 15% to 30%: Not recommendedAntimycobacterials Rifampin Levels: NVP 37% Levels: DLV 96% Levels: EFV 25% Not recommended Contraindicated No dose adjustment Rifabutin Levels: NVP 16% Levels: DLV 80% Levels: EFV unchanged No dose change RBT 35% RBT 100% Not recommended Dose: RBT to 450 mg/day 2x to 3x/week EFV dose - standard Clarithromycin Levels: clarithromycin 39% Levels: NVP 26% Levels: clarithromycin 100% Alternative recommended Clarithromycin 30% DLV 44% Dose: standard Dose: adjustment for renal failureOral Contraceptives No data Ethinylestradiol 20%, use Levels: Ethinylestradiol 37% alternative method Use alternative method of birthAnticonvulsants Unknown Unknown, but may decrease DLV levels Unknown Phenobarbitol Monitor anticonvulsant level substantially Use with caution Phenytoin Monitor anticonvulsant levels Monitor anticonvulsant levels CarbamazepineMethadone NVP unchanged No data Methadone levels decreased - Methadone 60% methadone dose Titrate methadone doseMiscellaneous May increase levels of dapsone, warfarin, Monitor warfarin when used co and quinidine Sildenafil: Do not exceed 25 mg/48 hoursTop of Page | Next page -- Table 4-22: Drug Interactions: Protease Inhibitors and Non-Nucleoside
    • Top of Page | Next page -- Table 4-22: Drug Interactions: Protease Inhibitors and Non-Nucleoside Transcriptase Inhibitors Effect of Drug on Levels (AUCs)/DoseCopyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rightsreserved.* Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained inthis site because no single reference or service can take the place of medical training, education, and experience. Consumers arecautioned that this site is not intended to provide medical advice about any specific medical condition they may have or treatmentthey may need and they are encouraged to call or see their physician or other health care provider promptly with any health relatedquestions they may have.
    • Go to a Chapter Table of Contents Natural History and Classification Tests Disease Prevention Antiretroviral Therapy Management of Opp Infections Drugs: Guide to Information Systems Review HIV in CorrecIV. Antiretroviral Therapy Recommendations for Antiretroviral Therapy Goals of Therapy Terms and Concepts Antiretroviral Therapy for HIV Infected Patients Recommendations for Antiretroviral Therapy in Pregnancy Postexposure Prophylaxis for Health Care Workers Postexposure Prophylaxis for Sexual Contact or Needle Sharing Antiretroviral Agents Nucleoside Analogs Non-nucleoside Reverse Transcriptase Inhibitors (NNRTI) Protease Inhibitors Class Adverse Reactions to Antiretroviral Agents Tables Table 4-16: Antiretroviral Drugs Approved by FDA for HIV Table 4-20: Drugs That Should Not be Used with Protease Inhibitors or NNRTIs* Table 4-21: Drug Interactions Requiring Dose Modifications or Cautious Use Table 4-22: Drug Interactions: Protease Inhibitors and Non-Nucleoside Reverse Transcriptase InhibitorsEffect of Drug on Levels (AUCs)/Dose Table 4-27: HIV-Related Drugs with Overlapping Toxicities Table 4-28: Dosing of Antiretroviral Agents in Renal and Hepatic Failure Table 4-29: Characteristics of Antiretrovirals During Dialysis II. Antiretroviral Agents
    • Table 4-22: Drug Interactions: Protease Inhibitors and Non-Nucleoside Reverse TranscriptaEffect of Drug on Levels (AUCs)/DoseDrug Affected RTV SQV NFV APVIDV Levels: IDV no effect Levels: IDV 38% Levels: IDV 2x to 5x Levels: IDV 50% Dose: IDV 400 mg SQV 4x to 7x APV 33% NFV 80% bid/RTV 400 mg bid, or Dose: Insufficient data Dose: IDV 800 mg tid, Dose: limited data for IDV IDV 800 mg bid + RTV APV 800 mg tid 1200 mg bid + NFV 1250 100 bid mg bidRTV - Levels: RTV no effect Levels: RTV no effect Levels: APV 2.5x; RTV SQV 20x* NFV 1.5x no change Dose: Invirase or FTV Dose: RTV 400 mg bid + Dose: APV 600 to 1200 400 mg bid + RTV 400 NFV 500 to 750 mg bid mg bid + RTV 100 to 200 mg bid; FTV 1000 mg mg bid or APV 1200 mg bid + RTV 100 mg bid qd + RTV 200 mg qd (limited clinical data)SQV - - Levels: APV 32% Levels: SQV 3x to 5x SQV 19% NFV 20% Dose: SQV 800 mg tid, Dose: standard NFV + APV 800 mg tid (limited FTV 800 mg tid or 1x200 data) bidNFV - - - Levels: NFV 15% APV 1.5x Dose: NFV 750 mg tid, APV 800 mg tid (insufficent data)APV - - - -* Conducted with Invirase Conducted with FTVTable 4-22: Drug Interactions: Protease Inhibitors and Non-Nucleoside Reverse TranscriptaEffect of Drug on Levels (AUCs)/DoseDrug Affected NVP DLV EFVIDV Levels: IDV 28% Levels: IDV 31% Levels: IDV 40%; NVP no effect DLV: no effect Dose: IDV 1000 mg q8h; Dose: IDV 1000 mg q8h; Dose: IDV 600 mg q8h; EFV 600 mg hours standard NVP standard DLVRTV Levels: RTV 11% Levels: RTV 70% Levels: RTV 18% NVP no effect DLV no effect Dose: Standard for EFV 21% Dose: No data both drugs Dose: RTV 600 mg bid (5 intolerance); EFV 600 mgSQV Levels: SQV 25% Levels: SQV 62% Levels: SQV 5x NVP no effect DLV no effect EFV 12% Dose: No data Dose: FTV 800 mg tid, standard DLV Coadministration not reco (monitor transaminase levels)NFV Levels: NFV 10% Levels: NFV 2x NVP no effect DLV 50% Dose: Standard for Levels: NFV 20% Dose: NFV 1250 mg bid both drugs DLV 600 mg bid (limited data); monitor for Dose: Standard for neutropenic complications both drugs
    • APV No data No data APV 36%; Dose: APV 1200 mg tid a 1200 mg bid + RTV 200 m mg qd LPV/RTV Levels: LPV 55% No data Levels: LPV 40% Dose: LPV/RTV 533/133 EFV no change mg (4 caps) bid standard Dose: LPV/RTV 533 NVP (limited data) caps) bid + EFV 600 * Conducted with Invirase Conducted with FTV Top of Page | Next page -- Class Adverse Drug Reactions to Antiretroviral AgentsCopyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rightsreserved.* Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained inthis site because no single reference or service can take the place of medical training, education, and experience. Consumers arecautioned that this site is not intended to provide medical advice about any specific medical condition they may have or treatmentthey may need and they are encouraged to call or see their physician or other health care provider promptly with any health relatedquestions they may have.
    • Go to a Chapter Table of Contents Natural History and Classification Tests Disease Prevention Antiretroviral Therapy Management of Opp Infections Drugs: Guide to Information Systems Review HIV in CorrecIV. Antiretroviral Therapy Recommendations for Antiretroviral Therapy Goals of Therapy Terms and Concepts Antiretroviral Therapy for HIV Infected Patients Recommendations for Antiretroviral Therapy in Pregnancy Postexposure Prophylaxis for Health Care Workers Postexposure Prophylaxis for Sexual Contact or Needle Sharing Antiretroviral Agents Nucleoside Analogs Non-nucleoside Reverse Transcriptase Inhibitors (NNRTI) Protease Inhibitors Class Adverse Reactions to Antiretroviral Agents Tables Table 4-16: Antiretroviral Drugs Approved by FDA for HIV Table 4-20: Drugs That Should Not be Used with Protease Inhibitors or NNRTIs* Table 4-21: Drug Interactions Requiring Dose Modifications or Cautious Use Table 4-22: Drug Interactions: Protease Inhibitors and Non-Nucleoside Reverse Transcriptase InhibitorsEffect of Drug on Levels (AUCs)/Dose Table 4-27: HIV-Related Drugs with Overlapping Toxicities Table 4-28: Dosing of Antiretroviral Agents in Renal and Hepatic Failure Table 4-29: Characteristics of Antiretrovirals During DialysisTable 4-27: HIV-Related Drugs with Overlapping ToxicitiesBone Marrow Suppression Peripheral Pancreatitis Nephrotoxicity Hepatotoxicity NeuropathyCidofovir ddI Cotrimoxazole Adefovir DLVCytotoxic Isoniazid ddI Aminoglycosides EFV chemotherapy d4T 3TC Amphotericin B FluconazoleDapsone ddc (children) Cidofovir IsoniazidFlucytosine (5-FC) Pentamidine Foscarnet KetoconazoleGanciclovir IDV NVPHU Pentamidine NRTIsInterferon- PIsPentamidine RBTPyrimethamine RIFRibavirinSulfadiazineTMP-SMX (high dose)TrimetrexateAZTTop of Page | Next page -- Table 4-28: Dosing of Antiretroviral Agents in Renal and Hepatitic Failu
    • Copyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rightsreserved.* Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained inthis site because no single reference or service can take the place of medical training, education, and experience. Consumers arecautioned that this site is not intended to provide medical advice about any specific medical condition they may have or treatmentthey may need and they are encouraged to call or see their physician or other health care provider promptly with any health relatedquestions they may have.
    • Go to a Chapter Table of Contents Natural History and Classification Tests Disease Prevention Antiretroviral Therapy Management of Opp Infections Drugs: Guide to Information Systems Review HIV in CorrecIV. Antiretroviral Therapy Recommendations for Antiretroviral Therapy Goals of Therapy Terms and Concepts Antiretroviral Therapy for HIV Infected Patients Recommendations for Antiretroviral Therapy in Pregnancy Postexposure Prophylaxis for Health Care Workers Postexposure Prophylaxis for Sexual Contact or Needle Sharing Antiretroviral Agents Nucleoside Analogs Non-nucleoside Reverse Transcriptase Inhibitors (NNRTI) Protease Inhibitors Class Adverse Reactions to Antiretroviral Agents Tables Table 4-16: Antiretroviral Drugs Approved by FDA for HIV Table 4-20: Drugs That Should Not be Used with Protease Inhibitors or NNRTIs* Table 4-21: Drug Interactions Requiring Dose Modifications or Cautious Use Table 4-22: Drug Interactions: Protease Inhibitors and Non-Nucleoside Reverse Transcriptase InhibitorsEffect of Drug on Levels (AUCs)/Dose Table 4-27: HIV-Related Drugs with Overlapping Toxicities Table 4-28: Dosing of Antiretroviral Agents in Renal and Hepatic Failure Table 4-29: Characteristics of Antiretrovirals During Dialysis
    • Table 4-28: Dosing of Antiretroviral Agents in Renal and Hepatitic FailureDrug Name Usual Adult Dosing for GFR Dosing for Dosing for Dsoing in Dosing in Dose >50mL/min GFR GFR Hemodialysis Peritoneal 10 to 50 <10 mL/min Dialysis mL/minAZT (Retrovir) 300 mg bid 300 mg bid 300 mg bid 300 mg qd 300 mg qd* 300 mg qdddI (Videx) Weight >60 kg Usual dose 50% of usual 25% of usual 25% of usual dose* 25% of usual dose: dose dose dose 400 mg qd or 200 mg bid Weight <60 kg, dose: 250 mg qd or 125 mg bidd4T (Zerit) Weight >60 kg, Usual dose Weight >60 Weight >60 kg, 25% of usual dose* 25% of usual dose: kg, dose: dose: dose* 40 mg bid 20 mg every 20 mg q24h. Weight <60 kg, 12 to 24 Weight <60 kg, dose: hours dose: 30 mg bid Weight <60 15 mg ever 24 kg, dose: hours 15 mg every 12 to 24 hoursddC (Hivid) 0.75 mg tid 0.75 mg tid 0.75 mg bid 0.75 mg qd 0.75 mg qd* 0.75 mg qd*3TC (Epivir) 150 mg bid 150 mg bid 150 mg qd 50 mg qd 25-50 mg qd* 150 mg x 1 then 50 mg qd*ABC (Ziagen) 300 mg bid Usual dose Usual dose Usual dose Usual dose Usual doseEFV (Sustiva) 600 mg qd Usual dose** Usual dose Usual dose 600 mg qd No dataNFV (Viramune) 200 mg qd x 14 Usual dose Usual dose Usual dose Usual dose Unlikely to be days then 200 removed in mg bid dialysis due to high protein bindingDLV (Rescriptor) 400 mg tid Usual dose Usual dose Usual dose Usual dose likely Unlikely to be likely likely removed in dialysis due to high protein bindingNFV (Viracept) 750 mg tid or Usual dose Usual dose Usual dose Usual dose likely No data: usual 1250 mg bid dose likelyRTV (Norvir) 600 mg bid Usual dose Usual dose Usual dose Usual dose likely No data: usual dose likelySQV (Invirase, FTV) Invirase 400 mg Usual dose Usual dose Usual dose Usual dose likely No data: usual bid likely likely dose likely FTV 1200 mg tid, 1600 mg qd or 400 mg bidAPV (Agenerase) 1200 mg bid Usual dose Usual dose Usual dose Usual dose likely Usual dose likely likely likelyLPV/RTV 400/100 mg Usual dose Usual Usual dose Usual dose Usual dose(Kaletra) bid dose likely likely likely likely*Administer daily dose after dialysis. There are limited or no data on dosing in renal failure; the major mechanism of elimination of these drugs is hepatic metabolism, and this accounts forecommendaton of standard doses.
    • Top of Page | Next page -- Table 4-29: Characteristics of Antiretrovirals During DialysisCopyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rightsreserved.* Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained inthis site because no single reference or service can take the place of medical training, education, and experience. Consumers arecautioned that this site is not intended to provide medical advice about any specific medical condition they may have or treatmentthey may need and they are encouraged to call or see their physician or other health care provider promptly with any health relatedquestions they may have.
    • Go to a Chapter Table of Contents Natural History and Classification Tests Disease Prevention Antiretroviral Therapy Management of Opp Infections Drugs: Guide to Information Systems Review HIV in CorrecIV. Antiretroviral Therapy Recommendations for Antiretroviral Therapy Goals of Therapy Terms and Concepts Antiretroviral Therapy for HIV Infected Patients Recommendations for Antiretroviral Therapy in Pregnancy Post-exposure Prophylaxis for Health Care Workers Post-exposure Prophylaxis for Sexual Contact or Needle Sharing Antiretroviral Agents Nucleoside Analogs Non-nucleoside Reverse Transcriptase Inhibitors (NNRTI) Protease Inhibitors Class Adverse Reactions to Antiretroviral Agents Tables Table 4-16: Antiretroviral Drugs Approved by FDA for HIV Table 4-20: Drugs That Should Not be Used with Protease Inhibitors or NNRTIs* Table 4-21: Drug Interactions Requiring Dose Modifications or Cautious Use Table 4-22: Drug Interactions: Protease Inhibitors and Non-Nucleoside Reverse Transcriptase InhibitorsEffect of Drug on Levels (AUCs)/Dose Table 4-27: HIV-Related Drugs with Overlapping Toxicities Table 4-28: Dosing of Antiretroviral Agents in Renal and Hepatic Failure Table 4-29: Characteristics of Antiretrovirals During Dialysis
    • Table 4-29: Charateristics of Antiretrovirals During Dialysis Volume of Distribution Protein Binding Size (Molecular Weight) Prediction Based on Drug Charac AZT (Retrovir) 1.6 L/kg 34% to 38% 267 Dalton Not dialysed out ddI (Videx) 0.8 to 1 L/kg <5% 236 Dalton Dialysed out d4T (Zerit) 0.5 to 1 L/kg <5% 224 Dalton Likely to be dialysed out ddC (Hivid) 0.54 to 0.64 L/kg <4% 211 Dalton Likely to be dialysed out 3TC (Epivir) 0.9-1 to 7 L/kg <36% 229 Dalton Dialysed out ABC (Ziagen) 0.86 L/kg 50% 671 Dalton Not dialysed out EFV (Sustiva) 2 to 4 L/kg (in animal studies) 99.5% to 99.75% 315 Dalton Unlikely to be dialysed out NVP (Viramune) 1.4 L/kg 50% to 60% 266 Dalton Dialysed out with polysulfone memb DLV (Rescriptor) No data 60% (variable) 522 Dalton Low probability of small amount bein NFV (Viracept) 2 to 7 L/kg 99% 663 Dalton Unlikely to be dialysed out IDV (Crixivan) 4 L/kg 60% (variable) 712 Dalton Not dialysed out SQV (Invirase, Fortovase) 10 L/kg 98% 767 Dalton Not dialysed out LPV (Kaletra) No data 98% to 99% 620 Dalton Unlikely to be dialysed out APV (Agenerase) 16.4 L/kg 90% 508 Dalton Unlikely to be dialysed out Vd>Protein Binding>Size Likely to be removed Vd <0.7 L/kg Protein Binding <80% Size <1,500 Dalton Unlikely to be removed Vd >0.7 L/kg Protein Binding >80% Size >1,500 Dalton Top of Page | Next page -- Chapter V: Management of Opportunistic InfectionsCopyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rightsreserved.* Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained inthis site because no single reference or service can take the place of medical training, education, and experience. Consumers arecautioned that this site is not intended to provide medical advice about any specific medical condition they may have or treatmentthey may need and they are encouraged to call or see their physician or other health care provider promptly with any health relatedquestions they may have.
    • Go to a Chapter Table of Contents Natural History and Classification Tests Disease Prevention Antiretroviral Therapy Management of Opp Infections Drugs: Guide to Information Systems Review HIV in CorrecV. Management of Opportunistic Infections and Other Complications of HIV InfectionOpportunistic Infections Table 5-1: Fungal Pneumocystis carinii, Aspergillosis, Candidiasis, Cryptococcal meningitis, Cryptococcus without meningitis, HistoplasmoCoccidioidomycosis, Penicilliosis marneffei Table 5-2: Parasitic Infections Toxoplasma gondii, Cryptosporidiosis, Isosporidiosis, Microsporidiosis, Entamoeba histolytic Table 5-3: Mycobacterial Infections M. tuberculosis, M. avium, M. kansasii, M. haemophilum, M. gordonae, M. genavense, M. xenopimalonoense, M. chelonei Table 5-4: Viruses Herpes simplex, Herpes zoster, Cytomegalovirus retinitis, Progressive multifocal leukoencephalopathy Table 5-5: Bacteria Streptococcus pneumoniae, Bartonella henselea/ quintana, Haemophilus influenzae, Nocardia asteroidePseudomonas aeruginosa, Rhodococcus equi, Salmonella, Staphylococcus aureus, Treponema pallidum Table 5-6: Treatment of Miscellaneous and Non-Infectious Disease Complications/Classified by Organ Syste Table 5-6A: Cardiac Table 5-6H: Gastrointestinal Table 5-6B: Pulmonary Table 5-6I: Hepatobiliary Table 5-6C: Renal Table 5-6J: Wasting Table 5-6D: Neurologic Table 5-6K: Pain Table 5-6E: Hematologic Table 5-6L: Psychiatric and Sleep Disorders Table 5-6F: Tumors Table 5-6M: Terminal Illness Table 5-6G: Dermatologic V. Opportunistic InfectionsTable 5-1: FUNGAL INFECTIONS Preferred Regimen(s) Alternative Regimen(s)
    • Pneumocystis cariniipneumonia Acute infection TMP 15 mg/kg/day/SMX 75 TMP 15 mg/kg/day PO + dapsone mg/kg/day PO or IV x 21 days in 100 mg/day PO x 21 days 3 to 4 divided doses (typical oral dosage is 2 DS tid). Pentamidine 4 mg/kg/day IV x 21 days (usually reserved for severe cases) Clindamycin 600 mg IV q8h or 300 - 450 mg PO q6h + primaquine* 15-30 mg/day base PO x 21 days Atovaquone 750 mg suspension PO with meal bid x 21 days Trimetrexate 45 mg/m2/day IV plus folinic acid 20 mg/m2 PO or IV q6h.
    • Prophylaxis, initiation Dapsone 100 mg PO qdand discontinuation TMP/SMX PO (1 DS/day, 1 SS/day) Aerosolized pentamidine 300 mg q month via Respirgard II nebulizer ± ß2 Gradual initiaion using liquid agonist (albuterol, 2 puffs) formulation (40 mg TMP & 200 SMX/mL); Dapsone 50 mg/day PO plus Days 1 to 3: 1 mL pyrimethamine 50 mg/week PO + Days 4 to 6: 2 mL leucovorin 25 mg/week PO or Days 7 to 9: 5mL dapsone 200 mg + pyrimethamine 75 Days 10 to 12: 10mL mg + leucovorin 25 mg PO q week Days 13 to 14: 20 mL Day 15: DS tab Atovaquone 1500 mg qd TMP-SMX, 1DS 3x/week Other regimens without established efficacy: Dapsone 50 mg/day PO, pentamidine 4 mg/kg IM or IV q 4 weeks, Fansidar 1-2x/week.
    • Preferred Regimen(s) Alternative Regimen(s)Aspergillosis Amphotericin B 0.7-1.4 Itraconazole 200 mg PO tid x 3 days, Invasive pulmonary mg/kg/day then 400 mg/day as caps with meal +infection acidic drink or 200-400 mg/day solution on empty stomach. Lipid formulation of amphotericin: Amphotec, Abelcet or AmBisome Surgery for localized disease Caspofungin 70 mg IV day 1, then 50 mg IV qd Preferred Regimen(s) Alternative Regimen(s)
    • Candidiasis Clotrimazole oral troches 10 mg Oropharyngeal 5x/day Nystatin 500,000 units gargled 4-5x (thrush) day Initial infection Fluconazole 100 mg/day PO Itraconazole 100 mg/day oral suspension swished or swallowed, empty stomach Amphotericin B oral suspension 1-5 mL qid swish & swallow. No longer available commercially, but can be prepared by pharmacist with 100 mg/mL. Amphotericin B 0.3-0.5 mg/kg/day IV
    • Maintenance Clotrimazole (above dose), (optional or as needed: Nystatin (above dose) Fluconazole 100 mg/day PO or 200see Comment) mg 3x/week Itraconazole 200 mg /day as caps with meals + acidic drink or 100-200 mg/day solution on empty stomach Ketoconazole 200 mg/day PO
    • Prophylaxis Not recommended Preferred Regimen(s) Alternative Regimen(s)Vaginitis Intravaginal miconazole Ketoconazole 200 mg/day PO or bid suppository 200 mg x 3 days or x 5 to 7 days or 200 mg PO bid x 3 cream (2%) x 7 days days Clotrimazole cream (1%) x 7 to 14 days or tabs: 100 mg qd x 7 days or 100 mg x 2/day x 3 days or 500 mg x 1 Fluconazole 150 mg PO x1 Preferred Regimen(s) Alternative Regimen(s)Esophagitis: Fluconazole 200 mg/day PO;Initial infection up to 400 mg/day x 2 to 3 weeks Itraconazole 200 mg PO as caps with meal + acidic drink or 100-200 mg/day oral solution on empty stomach Amphotericin B IV 0.3-0.6 mg/kg/day x 10 to 14 days Caspofungin 70 mg IV day 1, then 50 mg IV/day.
    • Maintenance Fluconazole 100-200 mg/day PO Itraconazole 200 mg/day PO as caps (with food + acidic drink) or 100-200 mg/day oral solution on empty stomach Preferred Regimen(s) Alternative Regimen(s)Cryptococcalmeningitis Amphotericin B 0.7-1.0 Amphotericin B 0.7-1.0 mg/kg/day IV Initial treatment (NIAID mg/kg/day IV + 5-FC 100 (without 5-FC) x 14 days, thenMycosis Study Group mg/kg/day x 14 days PO fluconazole 400 mg/day x 8 to 10recommendations Clin ("Induction phase"), then weeks.Infect Dis 2000;30:710) fluconazole 400 mg/day x 8 to 10 weeks ("consolidation phase"), Fluconazole 400-800 mg/day PO + then maintenance therapy 200 5-FC 100 mg/kg/day PO x 6 to 10 mg/day ("suppressive phase") weeks. See comments regarding AmBisome 4 mg/kg/day IV x 14 management of elevated days, then fluconazole 400 mg/day x 8 intracranial pressure. to 10 weeks
    • Maintenance therapy Fluconazole 200 mg/day PO Amphotericin B 1.0 mg/kg/week Fluconazole: May increase maintenance dose to 400 mg/day Itraconazole 200 mg PO bid as caps with meal + acidic drink or 100 - 200 mg PO bid solution on empty stomach Preferred Regimen(s) Alternative Regimen(s)
    • Cryptococcosis without Fluconazole 200-400 mg/day Itraconazole 200 mg PO bid as capsmeningitis (pulmonary, PO indefinitely unless immune with meal + acidic drink or 100-200disseminated or reconstitution is achieved. mg/day bid oral suspension on emtpyantigenemia) stomach indefinitely unless immune reconstitution is achieved. Maintenance Fluconazole 200 mg/day PO Itraconazole 200 mg/day as caps (see comment) with meal + acidic drink or 100-200 mg/day oral suspension on empty stomach Amphotericin B 0.6-1 mg/kg IV weekly or 2x/week Preferred Regimen(s) Alternative Regimen(s)
    • Histoplasmosis Amphotericin B 0.7-1.0 Fluconazole 800 mg/day Disseminated initial mg/kg/day IV >3 to 14 daystreatment AmBisome 3-5 mg/kg/day IV Itraconazole 200 mg PO tid x 3 days, then 200 mg PO bid as caps with meal + acidic drink or 100-200 mg oral suspension on empty stomach bid x 12 weeks (mild-moderately severe disease)
    • Maintenance After amphotericin: Itraconazole Amphotericin B mg/kg 1x/week 200 mg PO tid x 3 days; then 200 mg bid as caps with meal + Fluconazole 800 mg/day PO acididc drink or solution 100-200 mg bid on empty stomach x 12 weeks, then 200-400 mg/day indefinitely as caps with meal or liquid on empty stomach. Monitor itraconazole levels and watch drug interactions. Prophylaxis Not generally recommended Itraconazole 200 mg/day PO Fluconazole 200 mg/day PO Preferred Regimen(s) Alternative Regimen(s)Coccidioidomycosis Amphotericin B mg/kg/day IVInitial treatment Fluconazole or itraconazole 400-800 mg/day
    • Maintenance Fluconazole 400 mg/day Itraconazole 400 mg/day Prophylaxis Not generally recommended Fluconazole or itraconazole 400 mg/day (see comment) Preferred Regimen(s) Alternative Regimen(s)Penicilliosis marneffei Amphotericin B (N Engl J Med 0.7-1.0 mg/kg/day1993;339:1739) Initial treatment Itraconazole 400 mg/day PO as caps with meal + acidic drink or solution on empty stomach. Maintenance Itraconazole Ketoconazole 200 mg/day PO
    • Top of Page | Next page -- Table 5-2: Parasitic Infections IndexCopyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rights reserved.* Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained in this site because noservice can take the place of medical training, education, and experience. Consumers are cautioned that this site is not intended to provide medical advspecific medical condition they may have or treatment they may need and they are encouraged to call or see their physician or other health care providany health related questions they may have.
    • Go to a Chapter Table of Contents Natural History and Classification Tests Disease Prevention Antiretroviral Therapy Management of Opp Infections Drugs: Guide to Information Systems Review HIV in CorrecV. Management of Opportunistic Infections and Other Complications of HIV InfectionOpportunistic Infections Table 5-1: Fungal Pneumocystis carinii, Aspergillosis, Candidiasis, Cryptococcal meningitis, Cryptococcus without meningitis, HistoplasmoCoccidioidomycosis, Penicilliosis marneffei Table 5-2: Parasitic Infections Toxoplasma gondii, Cryptosporidiosis, Isosporidiosis, Microsporidiosis, Entamoeba histolytic Table 5-3: Mycobacterial Infections M. tuberculosis, M. avium, M. kansasii, M. haemophilum, M. gordonae, M. genavense, M. xenopimalonoense, M. chelonei Table 5-4: Viruses Herpes simplex, Herpes zoster, Cytomegalovirus retinitis, Progressive multifocal leukoencephalopathy Table 5-5: Bacteria Streptococcus pneumoniae, Bartonella henselea/ quintana, Haemophilus influenzae, Nocardia asteroidePseudomonas aeruginosa, Rhodococcus equi, Salmonella, Staphylococcus aureus, Treponema pallidum Table 5-6: Treatment of Miscellaneous and Non-Infectious Disease Complications/Classified by Organ Syste Table 5-6A: Cardiac Table 5-6H: Gastrointestinal Table 5-6B: Pulmonary Table 5-6I: Hepatobiliary Table 5-6C: Renal Table 5-6J: Wasting Table 5-6D: Neurologic Table 5-6K: Pain Table 5-6E: Hematologic Table 5-6L: Psychiatric and Sleep Disorders Table 5-6F: Tumors Table 5-6M: Terminal Illness Table 5-6G: Dermatologic V. Opportunistic InfectionsTable 5-2: PARASITIC INFECTIONS
    • Toxoplasma gondii Pyrimethamine 100-200 mg loading Pyrimethamine + folinic Clinical improvemenencephalitis dose, then 50-100 mg/day PO + folinic acid (see preferred within 1 week and im Acute infection acid 10 mg/day PO + sulfadiazine for at regimen) + clindamycin by CT scan or MRI w least 6 weeks 900-1200* mg IV q6h or weeks. Failure to res 300-450 mg PO q6h for at and/or uncertain diag least 6 weeks usually an indication stereotactic brain bio Pyrimethamine and folinic yields a definitive dia acid (see preferred 98% of cases (Clin In regimen) plus one of the 2000;30:49). following: azithromycin 1200-1500 mg/day, Corticosteroids if si clarithromycin 1 g bid, or edema/mass effect ( atovaquone 750 mg qid with mg PO or IV q6h). food Pyrimethamine usu Azithromycin 900 mg PO x as a loading dose of 2 first day, then 1200 followed by 50 mg/da mg/day x 6 weeks, then 600 folinic acid 10 mg/da mg/day (patients <50 kg receive half dose) (salvage Controlled trial in 34 therapy) showed pyrimethami mg/day) plus sulfadia Experimental: mg/day x 8 weeks, th Azithromycin, g/day) was superior t clarithromycin, trimetrexate, pyrimethamine (50 m doxycycline, atovaquone clindamycin (2.4 g/da weeks, then 1.2 g/da Azithromycin for IV use: Infect Dis 1996;22:26 500 mg x 2 first day, then 500 mg/day x 9 days, then oral regimen. Suppressive Pyrimethamine 25-65 mg PO qd + folinic Pyrimethamine 25-65 Regimens with esta therapy acid 10 qd + sulfadiazide 0.5-1.0 g PO qid mg/day PO + folinic acid efficacy are pyrimeth 10-25 mg qd + clindamycin sulfonamide or clinda 300-450 mg PO q6h-q8h Pyrimethamine-sulf Alternatives without TMP-SMX, and atova established efficacy: pyrimethamine provid Pyrimethamine 25-65 P. carinii prophylaxis mg/day PO + folinic acid pyrimethamine-clinda 10-25 mg qd + either does not. atovaquone 750 mg q8h-q12h, dapsone 100 Patients who respo mg/day PO or azithromycin primary therapy shou 600 mg/day PO life-long suppressive The role of immune reconstitution in mod rule is unclear. Immu reconstitution: consid discontinuation when count >200/mm3 >3 m viral load <5000 c/mL CROI, San Francisco February 2000, Abst
    • Prophylaxis TMP-SMX 1 DS PO qd TMP-SMX 1 SS/day PO or Indications: Patien(See comment) 1 DS 3x/week positive toxoplasmos serology plus CD4 ce Dapsone 50 mg/day + nadir of <100/mm3 . pyrimethamine 50 mg/week + folinic acid 25 mg/week Efficacy for prophyl established for TMP- Dapsone 200 mg/week PO dapsone/pyrimetham + pyrimethamine 75 Preliminary data sho mg/week PO + folinic acid dapsone or atovaquo 25 mg/week PO effective (CPCRA 03 277). Other regimens without established efficacy: Pyrimethamine 25 m pyrimethamine-clindamycin, is ineffective; efficacy atovaquone, azithromycin, PO qd is not establis clarithromycin, or pyrimethamine-sulfadoxine Efficacy of TMP-SM (Fansidar) qd may be superior t lower dose. Immune reconstitu recommendations November 2001): Pri prophylaxis: Disconti prophylaxis when CD count is >200/mm3 fo months; restart when <100-200/mm3 . Seco prophylaxis: Disconti prophylaxis when CD count is >200/mm3 > completed initial ther asymptomatic for toxoplasmosis. Preferred Regimen(s) Alternative Regimen(s) Comment
    • Cryptosporidiosis Paromomycin 500 mg PO tid or 1000 mg Trials with paromom (See Clin Microbiol PO bid with food x 14 to 28 days, then only modest improve Nitazoxanide (UnimedReviews 500 mg PO bid no cures (Am J Med Pharmaceuticals, Buffalo1999;12:554; Clin 1996;100:370). Grove, Ill.) 500 mg PO bidInfect Dis Paromomycin 1 gm bid/azithromycin 6002001;32:331) mg qd x 4 weeks, then paromomycin An uncontrolled tria alone x 8 weeks Octreotide (Sandostatin) paromomycin + azith 50-500 µg tid SC or IV at 1 showed good respon mcg/hour of clinical symptoms Symptomatic treatment with nutritional supplements and anti-diarrheal agents: excretion (J Infect Di Lomotil, loperamide, paregoric, bismuth Azithromycin 1200 mg x 2 1998;178:900). Azith subsalicylate (Pepto-Bismol) and PO first day, then 1200 alone is ineffective. deodorized tincture of opium mg/day x 27 days, then 600 mg/day Nitazoxanide is not approved by the FDA HAART clinical trial data, inc Atovaquone 750 mg PO ACTG 192, shows m suspension with meal bid no benefit. HAART with immun reconstitution is the m effective treatment ( 1998;351:256; AIDS 1998;12:35; J AIDS 2000;25:124). NSAIDS are someti useful. Nutritional supplem required for severe c Vivonex for TEN or p hyperalimentation. Clarithromycin or R prophylaxis for MAC prophylaxis may redu cryptosporidiosis (JA 1998;279:384). Preferred Regimen(s) Alternative Regimen(s) CommentIsosporiasis TMP-SMX PO bid (2 DS PO bid or 1 DS Pyrimethamine 50-75 Duration of high-do Acute Infection ( N tid) x 2 to 4 weeks mg/day PO + folinic acid is not well defined.Engl J Med 5-10 mg/day x 1 month1989;320:1044; ClinInfect Dis There has been one2001;32:331) report of refractory in responded to pyrime plus sulfadiazine (Dia Microbiol Infect Dis 1
    • Suppressive TMP-SMX 1-2 DS/day or 3x/week Pyrimethamine 25 mg + Some advocate tre treatment sulfadoxine 500 mg/week indefinitely unless th PO (1 Fansidar/week) immune recovery. Pyrimethamine 25 mg + folinic acid 5 mg/day Preferred Regimen(s) Alternative Regimen(s) CommentMicrosporidiosis Symptomatic treatment with nutritional Metronidazole 500 mg PO Efficacy of albenda(Clin Infect Dis supplements and anti-diarrheal agents tid established only for i2001;32:331) (Lomotil, loperamide, paregoric, etc.) involving Septata inte Atovaquone 750 mg PO which cause 10% to with meals bid (AIDS cases. Albendazole 400-800 mg PO bid x >3 weeks (S. intestinalis) 1996;10:619) Anecdotal success with itraconazole, flu Thalidomide 100 mg/day atovaquone, and me (AIDS 1995;9:658) (Infect Dis Clin N Am 1994;8:483). HAART with immun reconstitution is best especially for the 80% of cases involving E. (Lancet 1998;351:25 1998;12:35; J Clin M 1999;37:421; J AIDS 2000;25:124). Experimental drugs Fumagillin, TNP-470Entamoeba Metronidazole 750 mg PO or IV tid x 5 to Paromomycin 500 mg PO E. histolytica is resphistolytica 10 days, plus diiodohydroxyguin 650 mg tid x 7 days amebiasis - dysenter(Clin Infect Dis tid x 20 days or paromomycin 500 mg tid x abscesses. E. dispar2001;32:331) 7 days for over 90% of stool most labs do not use serologic or stool EIA distinguish the two ( Dis 2000;30:959; Clin 2000;30:955). Only histolytica causes dis requires therapy.
    • Top of Page | Next page -- Table 5-3: Mycobacterial InfectionsCopyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rights reserved.* Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained in this site because noreference or service can take the place of medical training, education, and experience. Consumers are cautioned that this site is not intended to provideadvice about any specific medical condition they may have or treatment they may need and they are encouraged to call or see their physician or other hprovider promptly with any health related questions they may have.
    • Go to a Chapter Table of Contents Natural History and Classification Tests Disease Prevention Antiretroviral Therapy Management of Opp Infections Drugs: Guide to Information Systems Review HIV in CorrecV. Management of Opportunistic Infections and Other Complications of HIV InfectionOpportunistic Infections Table 5-1: Fungal Pneumocystis carinii, Aspergillosis, Candidiasis, Cryptococcal meningitis, Cryptococcus without meningitis, HistoplasmoCoccidioidomycosis, Penicilliosis marneffei Table 5-2: Parasitic Infections Toxoplasma gondii, Cryptosporidiosis, Isosporidiosis, Microsporidiosis, Entamoeba histolytic Table 5-3: Mycobacterial Infections M. tuberculosis, M. avium, M. kansasii, M. haemophilum, M. gordonae, M. genavense, M. xenopimalonoense, M. chelonei Table 5-4: Viruses Herpes simplex, Herpes zoster, Cytomegalovirus retinitis, Progressive multifocal leukoencephalopathy Table 5-5: Bacteria Streptococcus pneumoniae, Bartonella henselea/ quintana, Haemophilus influenzae, Nocardia asteroidePseudomonas aeruginosa, Rhodococcus equi, Salmonella, Staphylococcus aureus, Treponema pallidum Table 5-6: Treatment of Miscellaneous and Non-Infectious Disease Complications/Classified by Organ Syste Table 5-6A: Cardiac Table 5-6H: Gastrointestinal Table 5-6B: Pulmonary Table 5-6I: Hepatobiliary Table 5-6C: Renal Table 5-6J: Wasting Table 5-6D: Neurologic Table 5-6K: Pain Table 5-6E: Hematologic Table 5-6L: Psychiatric and Sleep Disorders Table 5-6F: Tumors Table 5-6M: Terminal Illness Table 5-6G: Dermatologic V. Opportunistic InfectionsTable 5-3: MYCOBACTERIAL INFECTIONS
    • Mycobacterium TB TREATMENT RECOMMENDATIONStuberculosisTreatment Induction Maintenance Comment(MMWR RIF-based therapy (no current use of PIs or NNRTIs)1998;47[RR-20];MMWR 2000;49:185) 1. INH/RIF/PZA/EMB (or SM) INH/RIF daily or RIF-containing regimens prec daily x 2 months 2-3x/week x 18 weeks concurrent PIs or NNRTIs ex EFV, RTV, and RTV + SQV 2. INH/RIF/PZA/EMB (or SM) INH/RIF or 2-3x/week x Assess HIV at 3 month interv daily x 2 weeks, then 2-3x/week 18 weeks determine needs for ART x 6 weeks 3. INH/RIF/PZA/EMB (or SM) INH/RIF/PZA/EMB (or A 2-week wash-out period is 3x/week x 8 weeks SM) 3x/week x 4 months between the last RIF dose an of PI or NNRTIs RBT-based therapy (concurrent PI or NNRTI) 1. INH/RIF/PZA/EMB daily x 8 INH/RIF daily or 2x/week Monitor for RFB toxicity-arthr weeks x 18 weeks uveitis, leukopenia 2. INH/RIF/PZA/EMB daily x 2 INH/RIF daily or Dose modifications of RFB an weeks, then 2x/week x 6 weeks 2-3x/week x 18 weeks PIs/NNRTI when given concu see below RFB should not be given with DLV SM-based therapy (concurrent PI or NNRTI) 1. INH/SM/PZA/EMB daily x 8 INH/SM/PZA 2-3x/week x SM is contraindicated in preg weeks 30 weeks women 2. INH/SM/PZA/EMB daily x 2 INH/SM/PZA 2-3x/week x If SM cannot be continued for weeks, then 2-3x/week x 6 30 weeks add EMB and treatment shou weeks extended to 12 months APV = amprenavir , EFV = efavirez, EMB = ethambutol, IDV = indinavir, INH = isonazide, NFV = nelfinavir, PZA = p RBT = rifabutin, RIF = rifampin, SM = streptomycin Directly observed therapy (DOT) 2-3x/week preferred DOT Daily 2x/week INH 5 mg/kg 15 mg/kg (300 mg)* (900 mg)* RIF 10 mg/kg 10 mg/kg (600 mg)* (600 mg)* PZA 15-30 mg/kg 50-70 mg/kg (2 g)* (4 g)* SM 15 mg/kg 25-30 mg/kg (1 g)* (1 g)* EMB 15-25 mg/kg 50 mg/kg (2 g)* (4 g)* * Maximum dose RIF may be used with EFV, RTV, or RTV + SQV when there are no other PIs or NNRTIs. When EFV is given with RIF, increase E mg/day. For other PI and NNRTI regimens, use RFB with dose adjustments indicated below.
    • * Maximum dose RIF may be used with EFV, RTV, or RTV + SQV when there are no other PIs or NNRTIs. When EFV is given with RIF, increase E mg/day. For other PI and NNRTI regimens, use RFB with dose adjustments indicated below.Options for antiretroviral therapy: Regimen that does not contain a PI or NNRTI SM-based therapy with no use of rifamycins (see above) Rifabutin-based treatment with dose adjustments (MMWR 2000;49:185) PI or NNRTI Rifabutin IDV, 1000 mg q8h 150 mg/day or 300 mg 2x/week NFV, 1000 mg tid or 1250 mg bid 150 mg/day or 300 mg 2x/week APV, 1200 mg bid 150 mg/day or 300 mg 2x/week EFV, 600 mg qd 450 mg/day or 600 mg 2x/week RTV, standard 150 mg 2-3x/week NVP 200 mg bid 300 mg/day RTV, 400 mg/SQV, 400 mg bid 150 mg 2-3x/week LPV/RTV, 400/100 mg bid 150 mg qod No data: SQV - sgc (FTV) Contraindicated: SQV-hgc (Invirase), DLV Recommendation of D. Havlir & P. Barnes (N Engl J Med 1999;340:367): INH, EMB, and PZA 24 months. Possible regimen based on pharmacokinetic studies: EFV 800 mg/day + RIF 600 mg/day or 6 weekly In a trial of 25 co-infected patients given RFB and PI-containing regimens, all 25 became and culture-negative within 2 months, and response to HAART was also impressive (Clin Infect D 2000;30:779). Preferred Regimen(s) Alternative Regimen(s) CommentProphylaxis Indications: PPDINH-susceptible induration, high-riskstrain INH 300 mg/day PO + pyridoxine 50 RIF 600 mg PO qd x 4 months mg/day PO x 9 months exposure, or prior po PPD without treatme RIF 600 mg/day + PZA 20 INH 900 mg 2x/week + pyridoxine 50 mg/kg/day x 2 months RIF containing regi mg 2x/week x 9 months (DOT) have drug interaction PZA 15-30 mg/kg/day plus RFB with PIs and NNRTIs in place of RIF to permit preferred regimens a concurrent PI or NNRTI (see INH or short-course above table for doses) x 2 prophylaxis with PZA months RIF using dose adjustments shown i above table. RIF/PZA previously favored since it is as effective as INH for 9 months and the prob of completing the 2-m course is better (JAM 2000;283:1445). Ho there has subsequen been reports of seve
    • effective as INH for 9 months and the prob of completing the 2-m course is better (JAM 2000;283:1445). Ho there has subsequen been reports of seve hepatotoxicity includ deaths attributed to regimen, although n these patients had concurrent HIV infec (MMWR 2001;50;77 a consequence, this regimen is only recommended for HIV-infected patients are not expected to complete the 9 mont regimen and should monitored with CBC LFTs (bilirubin and transaminase levels baseline, 2, 4, and 6 weeks.INH-resistant RFB 600 mg/day PO + PZA 20 RIF 150-450 mg/day (dose The choice of RIFstrain mg/kg x 2 months based on concurrent PI or RFB depends on NNRTI) + PZA x 2 months concurrent HAART.Multiply-resistant Fluoroquinolone + PZA or EMB + Base decision onstrain PZA susceptibility tests a consultation with pub health officials.Immune Antituberculosis therapy + Usual presentationreconstitution TB anti-inflammatory agents Inflammatory reactio to 3 weeks after HAA despite initial respon antituberculosis ther with fever, lymph adenopathy, and increased pulmonary infiltrates. AFB stain cultures of sputum a nodes are negative ( 1998;114:933; Am J 1999;106:371; Clin I Dis 1998;26:1008; Respir Crit Care Med 1998;158:157). Clarithromycin 500 mg PO bid RFB 300 mg/day PO (adjust Indications: <50/mMycobacterium dose if given with PI or NNRTI) rule out MAC bacteravium complex and active TB. Azithromycin 1200 mg/week(MAC) Azithromycin 1200 mg/weekbacteremia Preliminary data su plus RBT 300 mg/day PO low-dose clarithromy (500 mg/day) may beProphylaxis: effective (AIDSinitiation and 1999;13:1367).discontinuation Azithromycin contrib to PCP prophylaxis b further reducing rate PCP (Lancet 1999;354:891).
    • Azithromycin contrib to PCP prophylaxis b further reducing rate PCP (Lancet 1999;354:891). Combination of azithromycin plus RF was associated with 85% reduction in the expected number of of disseminated MAC Engl J Med 1996;335:392). In 2 there was no appare benefit to adding RF clarithromycin for preventive treatment possibly due to the d interaction resulting reduced levels of clarithromycin (N En Med 1996; 335:428; Infect Dis 2000;181: Prophylaxis failure RFB usually involve clarithromycin-sensi strains; failures with clarithromycin or azithromycin often in clarithromycin-resist strains. The revised CDC/ID Guidelines (Novemb 2001) recommend: Primary prophylaxis: Discontinue when th CD4 cell count is >100/mm3 x >3 mon and restart when CD count is <50-100/mm Secondary prophyla Discontinue when C cell count is >100/m >6 months, complete months MAC therapy asymptomatic; resta when CD4 cell coun <100-200/mm3 .MAC bacteremia Clarithroymcin 500 mg PO bid plus Azithromycin 600 mg/day PO in Duration is indefini Treatment EMB 15 mg/kg/day PO place of clarithromycin + EMB + absence of immune RFB (same doses) reconstitution. With HAART, initial result suggest that MAC Combination treatment with treatment may be amikacin 10-15 mg/kg/day IV or discontinued when M ciprofloxacin 500-700 mg bid treatment is >1 yr, C cell count is >100/m 3 to 6 months and th patient is asymptom Infect Dis 1998;178: Clarithromycin leve
    • amikacin 10-15 mg/kg/day IV or discontinued when Mciprofloxacin 500-700 mg bid treatment is >1 yr, C cell count is >100/m 3 to 6 months and th patient is asymptom Infect Dis 1998;178: Clarithromycin leve increased 50% to 80 with concurrent administration of IDV RTV, and SQV; NFV APV have no effect o clarithromycin levels has not been studied Clarithromycin shou be given with EFV (s Table 4-21). In vitro susceptibilit tests are not useful i previously untreated patients (Clin Infect 1998;27:1369). In a comparative tr azithromycin vs clarithromycin for MA bacteremia clarithrom was superior in time negative blood cultu (Clin Infect Dis 1998;27:1278; see a Antimicrob Agents Chemother 1999;43:2869). Nevertheless, anoth large trial using azithromycin 600 mg vs clarithromycin 50 bid, each combined EMB, showed compa results (Clin Infect D 2000;31:1254). RBT: dose adjustm with RBT and concu PIs or NNRTI are summarized above - table above. Comparison of clarithromycin/EMB clarithromycin/EMB/ showed the three dru regimen had no clini benefit but decrease of clarithromycin resistance (J Infect D 1999;28:1080). Drug interaction be clarithromycin and R results in decreased levels of clarithromy Engl J Med 1996;335:428). RFB dose is 300 to
    • clarithromycin and R results in decreased levels of clarithromy Engl J Med 1996;335:428). RFB dose is 300 to mg/day, but should n exceed 300 mg/day given with clarithrom or fluconazole. Note interactions with PIs NNRTIs. ASA or NSAID ofte effective for symptom relief. Clarithromycin at a >1000 mg/day was associated with incre mortality (Ann Intern 1994;121:905). Immune reconstitut Suggested criteria to discontinue seconda prophylaxis (mainten therapy) are a CD4 c count >200/mm3 foll 6 to 12 months on H (J Infect Dis 1998;178:1446; 8th Chicago, Ill., Februa 2001, Abstract 547).Immune recovery Clarithromycin 500 mg bid + EMB 15 A zithromycin/EMB + RFB Characterized by hlymphadenitis mg/kg/day + RFB 300 mg/day po fever, leukocytosis, a Corticosteroids with rapid taper lymphadenopathy of for severe symptoms or draining involving the periaor sinuses and mesenteric node Biopsy shows granulomatous Surgical drainage may be lymphadenitis with A indicated. large numbers. Occu within 1 to 3 months HAART (Lancet 1998;351:252; J AID 1999;20:122; Ann In Med 2000;133:447). Other, less commo presentations: osteomyelitis, bursiti adrenal insufficiency nodules (Ann Intern 2000;133:447).Mycobacterium INH 300 mg/day PO + RIF 600 Also consider ciprofloxacin 750 Experience in HIVkansasii mg/day PO + EMB 25 mg/kg/day x 2 mg PO bid and clarithromycin infected patients is l(Am J Resp Crit months, then 15 mg/kg/day x 18 500 mg PO bid (J AIDS 1991; 4:516Care Med months (total) to life long therapy ± Intern Med 1991;1997;156:S1) SM 1 gm IM 2x/week x 3 months 114:861). Need in vitro sensi data.
    • kansasii mg/day PO + EMB 25 mg/kg/day x 2 mg PO bid and clarithromycin infected patients is l(Am J Resp Crit months, then 15 mg/kg/day x 18 500 mg PO bid (J AIDS 1991; 4:516Care Med months (total) to life long therapy ± Intern Med 1991;1997;156:S1) SM 1 gm IM 2x/week x 3 months 114:861). Need in vitro sensi data. Duration of treatme arbitrary - many trea HIV-infected patients life. Most strains are re to INH, but it is usua included in the regim with little supporting Immune reconstitut Reports of cervical a mediastinal adenopa osteonyelitis and art due to M. kansasii d the first 3 months of HAART.Mycobacterium INH/RIF/EMB Clarithromycin, doxycycline, Experience is limitehaemophilum ciprofloxacin, and amikacin are (Eur J Clin Microbiol active in vitro Dis 1993;12:114).Mycobacterium INH/RIF/clofazimine or clarithromycin SM may be useful Most isolates aregordonae contaminants (Dermatology 1993;187:301; AIDS 1992;6:1217; Antimi Agents Chemother 1992;36:1987).Mycobacterium Clarithromycin/EMB/RIF Other possible agents:genavense ciprofloxacin, amikacin, and PZA Clarithromycin-conta regimens are most effective (AIDS 1993;7:1357).M. xenopi INH; RIF, EMB and SMM. fortuitum Amikacin 400 mg q12h + cefoxitin 12 Duration of therapy g/day x 2 to 4 weeks, then oral agents months for cutaneou based on in vitro tests - clarithromycin lesions and >6 mont 1 g/day, doxycycline 200 mg/day, bone lesions in SMX 1 g tid, ciprofloxacin 500 mg bid. non-HIV-infected paM. malmoense RIF/INH/EMB See Clin Infect Dis 1993;16:540M. chelonae Clarithromycin 500 mg bid x >6 Variable activity - cefoxitin, Need in vitro months amikacin, doxycycline, imipenem, susceptibility test res tobramycin Often need combination Top of Page | Next page -- Table 5-4: Viruses
    • Top of Page | Next page -- Table 5-4: VirusesCopyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rights reserved.* Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained in this site because noor service can take the place of medical training, education, and experience. Consumers are cautioned that this site is not intended to provide medicalspecific medical condition they may have or treatment they may need and they are encouraged to call or see their physician or other health care providany health related questions they may have.
    • Go to a Chapter Table of Contents Natural History and Classification Tests Disease Prevention Antiretroviral Therapy Management of Opp Infections Drugs: Guide to Information Systems Review HIV in CorrecV. Management of Opportunistic Infections and Other Complications of HIV Infection Opportunistic Infections Table 5-1: Fungal Pneumocystis carinii, Aspergillosis, Candidiasis, Cryptococcal meningitis, Cryptococcus without meningitis, HistoplasmoCoccidioidomycosis, Penicilliosis marneffei Table 5-2: Parasitic Infections Toxoplasma gondii, Cryptosporidiosis, Isosporidiosis, Microsporidiosis, Entamoeba histolytic Table 5-3: Mycobacterial Infections M. tuberculosis, M. avium, M. kansasii, M. haemophilum, M. gordonae, M. genavense, M. xenopimalonoense, M. chelonei Table 5-4: Viruses Herpes simplex, Herpes zoster, Cytomegalovirus retinitis, Progressive multifocal leukoencephalopathy Table 5-5: Bacteria Streptococcus pneumoniae, Bartonella henselea/ quintana, Haemophilus influenzae, Nocardia asteroidePseudomonas aeruginosa, Rhodococcus equi, Salmonella, Staphylococcus aureus, Treponema pallidum Table 5-6: Treatment of Miscellaneous and Non-Infectious Disease Complications/Classified by Organ Syste Table 5-6A: Cardiac Table 5-6H: Gastrointestinal Table 5-6B: Pulmonary Table 5-6I: Hepatobiliary Table 5-6C: Renal Table 5-6J: Wasting Table 5-6D: Neurologic Table 5-6K: Pain Table 5-6E: Hematologic Table 5-6L: Psychiatric and Sleep Disorders Table 5-6F: Tumors Table 5-6M: Terminal Illness Table 5-6G: Dermatologic V. Opportunistic InfectionsTable 5-4: VIRUSES Preferred Regimen(s) Alternative Regimen(s) CommentHerpes simplex Initial treatment Mild Acyclovir 400 mg PO tid Failure to respond: give valacyclov or famciclovir 250 mg PO acyclovir IV. tid or valacyclovir 1.0 g PO bid; all given for 7 to 10 days. Early treatment shortens duration, r viral shedding, and reduces systemic it does not influence probability of re (Med Letter 1995;37:117).
    • Severe or refractory Acyclovir up to 800 mg Foscarnet 40 mg/kg IV Consider testing sensitivity of isolat PO 5x/day or 15-30 q8h or 60 mg/kg q12h x 3 acylovir; for resistant HSV: IV foscarn mg/kg/day IV at least 7 weeks trifluridine, oral valacyclovir, or high- days acyclovir (12-15 mg/kg IV q8h or by c Topical trifluridine as infusion). Relapses after treatment o 1% ophthalmic solution acyclovir-resistant strains often invol Valacyclovir 1 g PO bid q8h acyclovir-sensitive strains (N Engl J M 1991;325:551). Alternative topical agents: cidofovir 3% and Topical trifluridine solution (Viroptic foscarnet 1% cream applied after H2O2 cleansing and gen debridement; cover with non-absorba Cidofovir 5 mg/kg q 2 with Bacitracin and polymyxin ointme weeks (limited 1996;12:147). Topical foscarnet is av experience) from Astra and 3% topical cidofovir m prepared from the IV preparation (J I 1997;17:862; N Engl J Med 1993;327Recurrent Acyclovir 400 mg PO tid Early treatment is much more effec or 800 mg PO bid or Intern Med 1996;156:1729). famciclovir 125 mg PO bid or valacyclovir 500 mg PO bid; all given for 5 daysProphylaxis Acyclovir 400 mg PO Alternative is to treat each episode. bid or famciclovir 125-250 mg PO bid or Patients receiving ganciclovir, fosca valacyclovir 500 mg PO cidofovir do not require acyclovir pro bid or 1 g/day AIDS patients may require higher dVisceral Acyclovir 30 mg/kg/day Foscarnet 40 mg/kg IV Includes esophagitis and encephal IV at least 14 to 21 days q8h x >10 days may involve acyclovir resistant strain patients (J Infect Dis 1990;161:711). Valacyclovir 1 g PO tid Preferred Regimen(s) Alternative Regimen(s) Comment
    • Herpes zoster Acyclovir 800 mg PO Acyclovir 30 mg/kg/day Some authorities recommend cortic Dermatomal 5x/day at least 7 days IV Ann Intern Med 1996;125:376). Pred (until lesions crust) or mg x 7 days, 30 mg days 8 to 14, 15 famciclovir 500 mg PO tid Foscarnet 40 mg/kg IV to 21. or valacyclovir 1 g PO tid q8h or 60 mg/kg IV q12h x >7 days Postherpetic neuralgia is uncommo persons <55 years. Foscarnet preferred for acyclovir-re cases (N Engl J Med 1993;308:1448 Comparative trial of acyclovir vs val showed slight advantage to valacyclo (Antimicrob Agents Chemother 1995 Treatment can be started as long as lesions are forming. Pain control: gabapentin, trycyclics, carbamazepime, Lidocaine patch, na (effective and underused). Disseminated, Acyclovir 30-36 Foscarnet 40 mg/kg IV Role of maintenance therapy uncleophthalmic nerve mg/kg/day IV at least 7 q8h or 60 mg/kg q12hinvolvement or visceral days Ayclovir-resistant Foscarnet 40 mg/kg IV Cidofovir IV Foscarnet is drug of choice (Ann Instrains q8h or 60 mg/kg q12h 1991;115:9; J AIDS 1993;7:254). Topical trifluridine Maintenance Acyclovir, famciclovir, or Indication: Frequent recurrences.(see Comment) valacyclovir PO in above doses Prevention Varicella zoster immune Acyclovir 800 mg PO Indication: Exposure to chickenpo globulin (VZIG) 5 vials 5x/day x 3 weeks. shingles plus no history of either and (6.25 mL) within 96 hours available, negative VZV serology. Pr of exposure. treatment must be initiated within 96 (Note: Acyclovir has been removed from the exposure and preferrably within 48 h 1999 USPHS/IDSA guidelines for intraocular prophylaxis due to lack of documented efficacy.) Preferred Regimen(s) Alternative Regimen(s) Comment
    • Cytomegalovirus Intraocular ganciclovir Alternating or combining Median times to progression with inRetinitis implant (Vitrasert) q 6 foscarnet and ganciclovir treatment: Ganciclovir IV 47 to 104 d months + oral foscarnet IV 53 to 93 days, ganciclov Initial Treatment valganciclovir 900 Intraocular injections of IV 129 days, oral ganciclovir 29 to 53Recommendations of mg/day foscarnet 1.2-2.4 mg in ganciclovir implant Sp. intravitreal 21the IAS-USA (Arch 0.1 mL (N Engl J Med days, cidofovir IV 64 to 120 days, fomIntern Med Foscarnet 60 mg/kg IV 1994;330:868) or intravitreal injection 90 to 110 days.1998;158:957) q8h or 90 mg/kg IV q12h ganciclovir 2000 µg in x 14 to 21 days 0.05-0.1 mL (Br J Valganciclovir is a prodrug of ganci Ophthal 1996;80:214). preferred due to better absorption, 60 Ganciclovir 5 mg/kg IV to 9% for oral ganciclovir. bid x 14 to 21 days Fomivirsen, 330 mg by intravitreal injection day 1 Oral ganciclovir should not be used Valganciclovir 900 mg and 15, then monthly induction therapy. Maintenance with PO bid x 21 days, then ganciclovir is nearly as effective as IV 900 mg/day ganciclovir, but should be avoided w near the optic nerve or fovea (N Eng 1995;333:615). Valganciclovir in stan Cidofovir 5 mg/kg 1V q (900 mg) provides serum levels comp week x2, then 5 mg/kg q those achieved with IV ganciclovir 5 2 weeks + probenecid, 2 g PO 3 hours before each Foscarnet requires infusion pump, l dose, 1 g PO at 2 and 8 infusion time, saline hydration. hours post dose Ganciclovir implant + oral ganciclov equivalent to IV cidofovir (Am J Opht 2001;131:457). Vitrasert (intraocular ganciclovir rele device) was superior to IV ganciclovi relapse (220 days vs 71 days), but th increased risk of involvement of the o and increased risk of extraocular CM (N Engl J Med 1997;337:83). The sa applies to fomivirsen injections. Any therapy should be accompanied by s anti-CMV therapy such as oral ganci Engl J Med 1997;337:105). The Roch Ganciclovir Study showed that Vitras ganciclovir (4.5 g/day) was therapeu superior to IV ganciclovir (N Engl J M 1999;340:1063).
    • Progression or relapse Ganciclovir implant (if Cidofovir 5 mg/kg (as Time to relapse varies with definitio(on maintenance not used previously). above) retinal photographs, and treatmentastherapy) summarized above. Subsequent rela Induction dose of same agent Fomivirsen, 330 mg by more rapidly. (ganciclovir 10 mg/kg/day, or intravitreal injection day 1 foscarnet 180 mg/kg/day) or switch to alternative drug and 15, then monthly ACTG 228 showed no difference be (induction doses) reinduction with the same drug comp switching to the alternative drug. Wit Cidofovir (as combination treatment, there was the Combination treatment above)/oral ganciclovir, 1 outcome for time to progression (4.8 with ganciclovir/foscarnet g PO tid with meal 1.6 to 2.1 months) (Arch Ophthalmol in maintenance doses (J 1996;114:23). Infect Dis 1993;168:444; Am J Ophthalmol 1994;117:776; Arch Preliminary data for cidofovir/oral g Ophthalmol show good response rates and good 1996;114:23). effect, but high rates of drug-related (Clin Infect Dis 1999;28:528). IAS-USA revised recommendation - J Ophthalmol 1999;127:329): Gancic implant; prior exposure to ganciclovir associated with CMV ganciclovir resi failure to respond. If the ganciclovir i consider IV or intravitreal foscarnet.Maintenance Foscarnet 90-120 Indications: Life-long maintenance mg/kg/day IV required for retinitis in patients witho recovery. Initial studies with HAART Ganciclovir 5-6 discontinuation of CMV maintenance mg/kg/day IV 5-7 was safe in 30/30 patients with CD4 days/week or 1000 mg of 100-150/mm3 followed for 3 to 12 m PO tid (Clin Infect Dis 1999;28:528; Ophtha 1998;105:1259). Valganciclovir 900 mg Foscarnet maintenance dose is arb PO qd study showed that 120 mg/kg/day wa to 90 mg/kg/day with regard to surviv Cidofovir 5 mg/kg IV to progression (J Infect Dis 1993;167 every other week See above for median time to relap Intraocular ganciclovir different initial regimens. implant q 6 months + oral valganciclovir 900 Discontinuation: Several reports d mg/day safety of discontinuation of maintena for CMV retinitis when CD4 cell coun to >100-150/mm3 with no relapse in f periods of 30 to 90 weeks (JAMA 1999;282:1633). The largest report o discontinuation of CMV treatment is f RESTIMOP Study Team, which used of a CD4 cell count >75/mm3 and a v <30,000 c/mL. There was a retinitis r 1/48 with a median follow-up of 48 w 2001;15:23). The revised CDC/ISDA recommendations (November 2001) discontinue secondary prophylaxis w CD4 cell count is >100-150/mm , the 3 evidence of active disease, and there regular ophthalmologic exams; resta prophylaxis when CD4 cell count is
    • 2001;15:23). The revised CDC/ISDA recommendations (November 2001) discontinue secondary prophylaxis w CD4 cell count is >100-150/mm , the 3 evidence of active disease, and there regular ophthalmologic exams; resta prophylaxis when CD4 cell count is <100-150/mm . 3 Restart anti-CMV therapy if CD4 ce decreases again to <50/mm3 .Immune recovery vitritis Systemic or periocular Posterior segment inflammation in p corticosteroids with inactive CMV retinitis and immun associated with HAART (Arch Ophth 1998;116:169). May be complicated macular edema, epiretinal membrane papillitis. Incidence is highly variable: from 0.11/person-years to 0.86/person-ye Ophthalmol 2000;129:634; J Infect D 1999;179:697). Lower rate may be du CMV suppression before HaART sta Must exclude other causes of uveiti syphilis, toxoplasmosis, lymphoma, a reactions (Am J Ophthalmol 1998;12 Other expressions of CMV activati pancreatitis, submandibular adenopaCytomegalovirusExtraocular disease Ganciclovir 5 mg/kg IV Ganciclovir and foscarnet are equa Gastrointestinal for CMV colitis (Am J Gastroenterol bid x 3 to 6 weeks Failure: 1993;88:542). Ganciclovir/foscarnet Foscarnet 60 mg/kg q8h or 90 mg/kg IV q12h x 3 Maintenance therapy should be con to 6 weeks especially after re-induction and rela Role of oral ganciclovir is unclear. Patients should have regular ophtha screening. Foscarnet plus ganciclovir are asso poor quality of life (J Infect Dis 1993;
    • Neurologic disease Gaciclovir 5 mg/kg IV Ganciclovir 5 mg/kg IV Combination therapy with ganciclov bid x 3 to 6 weeks + bid x 3 to 6 weeks. foscarnet is probably optimal, but tole foscarnet 90 mg/kg IV bid poor and response is limited. One re x 3 to 6 weeks patients treated with this combination median survival of 3 months (AIDS 2000;14:517). Most important is imm reconstitution with HAART. Cidofovir: there is no experience wi neurologic disease. Treatment does not extend survival irreversible damage is often present treatment is started (Neurology 1996 Maintenance therapy should be giv induction phase.Pneumonitis Minimum diagnostic criteria: 1) pulm infiltrates; 2) detection of CMV with c Ganciclovir 5 mg/kg IV antigen or nucleic acid studies of pul bid >21 days secretions; 3) characteristic intracellu inclusions in lung tissue or BAL macr Foscarnet 60 mg/kg q8h and 4) absence of another pulmonar or 90 mg/kg IV q12h >21 (Arch Intern Med 1998;158:957). days Consider therapy if there is a co-pa fails to respond to therapy. Long-term maintenance therapy is u unnecessary unless there is relapse extrapulmonary end organ disease.
    • Progressive multifocal HAART Interferon alpha, 3 Diagnosis: PCR for JCV DNA is noleukoencephalopathy MU/day (see comment) of specific (J Infect Dis 1992;16:80;(PML) (JC Virus) 1992;66:5726). Positive PCR/typical MRI findings constitute presumptive PCR is negative, consider brain biop depending on probability of a treatab alternative diagnosis. Median surviva diagnosis is 2 to 4 months (J AIDS 1 N Engl J Med 1998;338:1345). In the largest series of patients with HAART (n=57), neurologic improvem seen in 26% and there was eradicati DNA in CSF in 57%. The authors not patients developed new PML after re HAART (J Infect Dis 2000;182:1077) have shown variable clinical and viro responses to HAART (AIDS 1999;13 Infect Dis 1999;28:1152; Clin Infect D 2000;30:95). Failed treatments in clinical trials in amantadine, adenosine arabinoside, arabinoside and intrathecal cytosine arabinoside (N Engl J Med 1998;338 Anecdotal reports suggest response interferon (J Neurovirol 1998;4:324). Initial trial with cidofovir (ACTG 363 no benefit. Top of Page | Next page -- Table 5-5: BacteriaCopyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rights reserved.* Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained in this site because noreference or service can take the place of medical training, education, and experience. Consumers are cautioned that this site is not intended to provideadvice about any specific medical condition they may have or treatment they may need and they are encouraged to call or see their physician or other hprovider promptly with any health related questions they may have.
    • Go to a Chapter Table of Contents Natural History and Classification Tests Disease Prevention Antiretroviral Therapy Management of Opp Infections Drugs: Guide to Information Systems Review HIV in CorrecV. Management of Opportunistic Infections and Other Complications of HIV InfectionOpportunistic Infections Table 5-1: Fungal Pneumocystis carinii, Aspergillosis, Candidiasis, Cryptococcal meningitis, Cryptococcus without meningitis, HistoplasmoCoccidioidomycosis, Penicilliosis marneffei Table 5-2: Parasitic Infections Toxoplasma gondii, Cryptosporidiosis, Isosporidiosis, Microsporidiosis, Entamoeba histolytic Table 5-3: Mycobacterial Infections M. tuberculosis, M. avium, M. kansasii, M. haemophilum, M. gordonae, M. genavense, M. xenopimalonoense, M. chelonei Table 5-4: Viruses Herpes simplex, Herpes zoster, Cytomegalovirus retinitis, Progressive multifocal leukoencephalopathy Table 5-5: Bacteria Streptococcus pneumoniae, Bartonella henselea/ quintana, Haemophilus influenzae, Nocardia asteroidePseudomonas aeruginosa, Rhodococcus equi, Salmonella, Staphylococcus aureus, Treponema pallidum Table 5-6: Treatment of Miscellaneous and Non-Infectious Disease Complications/Classified by Organ Syste Table 5-6A: Cardiac Table 5-6H: Gastrointestinal Table 5-6B: Pulmonary Table 5-6I: Hepatobiliary Table 5-6C: Renal Table 5-6J: Wasting Table 5-6D: Neurologic Table 5-6K: Pain Table 5-6E: Hematologic Table 5-6L: Psychiatric and Sleep Disorders Table 5-6F: Tumors Table 5-6M: Terminal Illness Table 5-6G: Dermatologic V. Opportunistic InfectionsTable 5-5: BACTERIA Preferred Regimen(s) Alternative Regimen(s) Comment
    • Streptococcus Penicillin, amoxicillin, Macrolide, vancomycinpneumoniae cefotaxime, ceftriaxone Treatment Susceptibility of S. pn (see Comment) based on CDC surveil with 3475 strains from Fluoroquinolone: States in 1998: penicil levofloxacin, moxifloxacin, resistance - 14%, mac or gatifloxacin. 11%, clindamycin - 3% doxycycline - 6%, fluoroquinolones - 0.2% Med 2000;343:1917). Strains highly resista penicillin should be tre vancomycin, linezolid, quinolones (levofloxac gatifloxacin, or moxiflo TMP-SMX is now cons inadequate for empiric high rates of resistanc Prevention CD4 cell count >200/mm 3 : None Repeat at 5-year inte pneumococcal vaccine 0.5 time of immune recove mL SC CD4 cell count >200 if vaccination was done CD4 cell count <200/mm 3 CD4 cell count was <2 consider vaccine Response with CD4 c <200/mm3 is reduced. In a controlled trial in Pneumovax was assoc higher rates of invasiv pneumococcal infectio 2000;355:2106). This led to controversy rega recommendation for P for HIV-infected perso Preferred Regimen(s) Alternative Regimen(s) CommentBartonella Erythromycin 500 mg PO Azithromycin 0.5-1 g/day PO x 1 to 3 Macrolide for MAC phenselae/quintana qid or doxycycline 100 mg months is protective.(bacillary PO bid x >3 months.angiomatosis andpeliosis hepatitis) Erythromycin or doxycycline + RIF 300 May require life-long mg IV or PO bid
    • Haemophilus Cefuroxime TMP-SMX Standard therapy usuinfluenzae adequate (Clin Infect D 2000;30:461). Cephalosporins, 2nd and 3rd generation H. influenzae vaccine is no recommended for adults bec infections involve non-encaps Fluoroquinolones that are not covered by the vNocardia Sulfadiazine or TMP-SMX 4 to 6 DS/day Treatment should conasteroides trisulfapyridine 4-8 g/day months PO or IV to maintain sulfa level at 15-20 mcg/mL Minocycline 100 mg PO bid Other suggested regimens: imipenem/amikacin; sulfonamide/amikacin or minocycline; ceftriaxone/amikacin.Pseudomonas Aminoglycoside + Monotherapy with antipseudomonas Antibiotic selection reaeruginosa antipseudomonal betalactum, ciprofloxacin, vitro susceptibility data beta-lactam (ceftazidime, aminoglycoside. cefoperazone, cefepime, ticarcillin, imipenem, piperacillin)Rhodococcus equi Vancomycin 2 g/day IV or Also sensitive to imipenem 2 g/day IV, aminoglycosides; resis usually combined with RIF to penicillins and ceph 600 mg/day PO, or ciprofloxacin 750 mg PO Duration of therapy is bid, or erythromycin PO or but relapses are comm IV x >1 month or until use prolonged oral ma infiltrate clears. therapy with macrolide fluoroquinolone. Resis these agents may devSalmonella Relapse is common. Acute (Clin Infect of Salmonella has beeDis 2001;32:331) Ciprofloxacin 500 mg PO TMP 5 to 10 mg/kg/day/SMX IV or 1 DS demonstrated only for bid x >2 weeks bid x >2 weeks ciprofloxacin. Ofloxacin 300 mg PO bid x Cephalosporins; 3rd generation >2 weeks AZT is active vs mos Salmonella strains and effective prophylaxis ( 1999;179:1553). Drug selection requir susceptibility data, esp ampicillin. TMP-SMX p sensitive. Maintenance Ciprofloxacin 500 mg PO TMP-SMX 5 mg/kg/day, TMP (1 DS PO Indications for mainte bid x several months bid) therapy, specific regim duration not well defin
    • Staphylococcus Antistaphylococcal Cephalosporin: first generation ± MRSA strains must baureus penicillin (nafcillin, oxacillin) gentamicin or RIF with vancomycin. ± gentamicin 1 mg/kg IV q8h or RIF 300 mg PO bid Vancomycin 1 g IV bid + gentamicin 1 Use of ciprofloxacin o mg/kg IV q8h x 3 days or RIF 300 mg PO quinolone requires in v Oral agents: Cephalexin bid sensitivity results 500 mg PO qid, dicloxacillin 500 mg PO qid, Linezolid 600 mg IV or PO bid Regimen and duratio ciprofloxacin 750 mg PO bid on site of infection and or clindamycin 300 mg PO sensitivity tests. qid Tricuspid valve endo oxacillin + gentamicin or oxacillin x 28 days + gentamicin x 3 days o ciprofloxacin 750 mg b 300 mg bid x 28 days.Treponema Primary secondary syphilis No alternative to penicillin considered Followup clinically anpallidum (syphilis) and early latent (<1 year): adequate for HIV-infected patients. With serologically primary a(MMWR benzathine penicillin G 2.4 a history of penicillin allergy, perform secondary cases at 3,1998;4[RR-1]:38) mil units IM weekly x1 (see skin test if reagents available (major and and 24 months; for late Comment) minor). If positive skin test or positive followup serology at 6, history and no skin test: desensitize. and 24 months Parenteral desensitization: 1 unit IV, Late latent syphilis (>1 then double dose at 15-minute intervals year or unknown): or increase dose 10-fold at 20- to A therapeutic trial of benzathine penicillin G 2.4 30-minute intervals. benzathine 2.4 mil uni mil units IM weekly x 3 primary or secondary s showed HIV-infected p responded less well se Neurosyphilis: Aqueous but clinical failures we penicillin G, 18-24 mil Engl J Med 1997; 337: units/day IV x 10 to 14 days (3-4 mil units q4h) Patients with latent s uncertain duration are to have late latent syp LP is recommended neurologic symptoms, failure, and late latent An ACTG trial showe ceftriaxone (2 g IV onc days) was equivalent t G (4 mil units IV q4h x neurosyphilis), but the were considered incon to a small sample size patients) and differenc patients in the two gro baseline (Clin Infect D 2000;30:540).
    • *Patients with severe forms of G6-PD deficiency are at risk for hemolytic anemia when given oxidant drugs such as dasulfonamides, and primaquine. Some advocate screening all potential recipients, some restrict screening to persons arisk (African-American men and men of Mediterranean descent, from India or from the Far East); some simply observeevidence of hemolysis, which usually occurs in first several days of treatment and often resolves with continued adminPatients with the Mediterranean variant are at risk for severe hemolysis . Ketoconazole and, to a lesser extent, itraconazole caps require gastric acid for absorption; absorption with hypochlobe enhanced by administration with 0.2 N HCI or the following soft drinks: Coca-Cola, Diet Coke, Pepsi, ginger ale anMinute Maid orange juice (Antimicrob Agents Chemother 1995;39:1671). The liquid formulation of itraconazole is prefcapsules for thrush, for patients with achlorhydria and those with subtherapeutic trough serum levels with capsules (<some consider the liquid formulation to be the preferred form for all oral itraconazole therapy, although all clinical trialthrush and Candida esophagitis were conducted with the capsule form. The liquid formulation should be taken on anstomach, which increases absorption by 50%; food increases absorption of intraconazo le caps by 50% (Drug InformaDI, Micromedex, 21 st edition, 2001, pg. 332). Top of Page | Next page -- Table 5-6: Treatment of Miscellaneous and Non-Infectious Disea Complications: Cardiac/Pulmonary/RenalCopyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rightsreserved.* Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained inthis site because no single reference or service can take the place of medical training, education, and experience. Consumers arecautioned that this site is not intended to provide medical advice about any specific medical condition they may have or treatmentthey may need and they are encouraged to call or see their physician or other health care provider promptly with any health relatedquestions they may have.
    • Go to a Chapter Table of Contents Natural History and Classification Tests Disease Prevention Antiretroviral Therapy Management of Opp Infections Drugs: Guide to Information Systems Review HIV in CorrecV. Management of Opportunistic Infections and Other Complications of HIV Infection Opportunistic Infections Table 5-1: Fungal Pneumocystis carinii, Aspergillosis, Candidiasis, Cryptococcal meningitis, Cryptococcus without meningitis, HistoplasmoCoccidioidomycosis, Penicilliosis marneffei Table 5-2: Parasitic Infections Toxoplasma gondii, Cryptosporidiosis, Isosporidiosis, Microsporidiosis, Entamoeba histolytic Table 5-3: Mycobacterial Infections M. tuberculosis, M. avium, M. kansasii, M. haemophilum, M. gordonae, M. genavense, M. xenopimalonoense, M. chelonei Table 5-4: Viruses Herpes simplex, Herpes zoster, Cytomegalovirus retinitis, Progressive multifocal leukoencephalopathy Table 5-5: Bacteria Streptococcus pneumoniae, Bartonella henselea/ quintana, Haemophilus influenzae, Nocardia asteroidePseudomonas aeruginosa, Rhodococcus equi, Salmonella, Staphylococcus aureus, Treponema pallidum Table 5-6: Treatment of Miscellaneous and Non-Infectious Disease Complications/Classified by Organ Syste Table 5-6A: Cardiac Table 5-6H: Gastrointestinal Table 5-6B: Pulmonary Table 5-6I: Hepatobiliary Table 5-6C: Renal Table 5-6J: Wasting Table 5-6D: Neurologic Table 5-6K: Pain Table 5-6E: Hematologic Table 5-6L: Psychiatric and Sleep Disorders Table 5-6F: Tumors Table 5-6M: Terminal Illness Table 5-6G: DermatologicTable 5-6: Treatment of Miscellaneous and Non-Infectious Disease Complications/ClassifiedOrgan SystemCondition Treatment Comment5-6A: CardiacCardiomyopathy ACE inhibitors such as enalapril -(J AIDS 2.5 mg bid titrated to 20 mg/day as Infectious causes: T. gondii, M. tuberculosis, C. neoforma1998;18:145) tolerated or captopril 6.25 mg tid increasing to 25-50 mg tid. Digitalis and diuretics are often added for Echocardiograms show dilated cardiomyopathy in up to 8 HIV-infected patients (N Engl J Med 1998;339:1093). In mo symptomatic left ventricular disease. biopsies reveal myocarditis and HIV nucleic acid sequence Some patients respond to suggesting a direct effect of HIV. Other possible etiologic m antiretroviral therapy (HAART) include immunologically mediated alterations, a role for oth cardiotrophic viruses or mitochondiral toxicity due to AZT a Use of NSAIDS and use of steroids NRTIs (Ann Intern Med 1992;116:311). are controversial. Subclinical cardiac abnormalities are common and correla extent of immune suppression (BMJ 1994;309:1605; N Eng 1998;339:1153).Pericardial Infection: bacterial, M. tuberculosis, Dx: Pericardiocentesis or biopsydisease MAC, C. neoformans, CMV Rx: Pericardiocentesis -- NSAIDs Tumor - Kaposis sarcoma, lymphoma Rx infection -- Avoid steroids
    • 5-6B: PulmonaryLymphoid HAART Possibly due to HIV infection of the lung.interstitialpneumonitis or Clinical presentation and X-ray resemble PCP, but CD4 cnon-specific Prednisone often 200-500. Many patients respond when inadvertentlyinterstitial PCP (Am J Respir Crit Care Med 1997;156:912).pneumonitis Indications and optimal dose of corticosteroid treatment n established; most initiate this treatment after initial observa progression; maintenance prednisone sometimes required patients become oxygen dependent.Pneumothorax Consider empiric treatment for P. PCP in 75% to 95% of cases (Chest 1991;100:1224; Che carinii 1994;108:946). Tube thoracostomy + pleurodesis5-6C: RenalHIV- Antiretroviral therapy (HAART) Most common biopsy finding is focal sgemental glomeruloassociated Presents with nephrosis and rapid course to end-stage rennephropathy Hemodialysis (Am J Kidney Dis in 1 to 4 months (Kidney 1995;48:311).(HIVAN) 1997;29:549). Hemodialysis and peritoneal dialysis appear equally Must distinquish from: 1)heroin-associated nephropathy, effective (Am J Kidney Dis far better prognosis; 2) acute tubular necrosis (including AT 1990;16:1). pentamidine, foscarnet, cidofovir, aminoglycosides); 3) IgA nephropathy; and 4) IDV-associated nephropathy (respond Prednisone 60 mg/day x 2 to 11 withdrawal). Features of HIVAN range from proteinuria and weeks, then taper 10 mg/week x 2 to hypoalbuminemia without hypertension, edema, to hyperlip 26 weeks large echogenic kidneys (Ann Intern Med 1990;112:35). Response to steroids is variable. The regimen in ACTG 2 ACE inhibitors such as captopril consisted of prednisone 60 mg/day x 6 weeks, then taper 1 6.25 - 25.0 mg PO tid (J Pediatr x 6 weeks. An uncontrolled trial of 60 mg/day x 2 to 11 wee 1991;119:710; J Am Soc Nephrol taper over 2 to 26 weeks showed decrease in creatinine in 1997;8:1140). decreased proteinuria in 12/13 (Am J Med 1996;101:41); 5 and responded to retreatment. Response to HAART based on clinical and biopsy data h reported (Lancet 1998;352:783).
    • Top of Page | Next page -- Treatment of Miscellaneous and Non-Infectious Disease Complicat NeurologicCopyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rights reserved.* Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained in this site because noreference or service can take the place of medical training, education, and experience. Consumers are cautioned that this site is not intended to provideadvice about any specific medical condition they may have or treatment they may need and they are encouraged to call or see their physician or other hprovider promptly with any health related questions they may have.
    • Go to a Chapter Table of Contents Natural History and Classification Tests Disease Prevention Antiretroviral Therapy Management of Opp Infections Drugs: Guide to Information Systems Review HIV in CorrecV. Management of Opportunistic Infections and Other Complications of HIV Infection Opportunistic Infections Table 5-1: Fungal Pneumocystis carinii, Aspergillosis, Candidiasis, Cryptococcal meningitis, Cryptococcus without meningitis, HistoplasmoCoccidioidomycosis, Penicilliosis marneffei Table 5-2: Parasitic Infections Toxoplasma gondii, Cryptosporidiosis, Isosporidiosis, Microsporidiosis, Entamoeba histolytic Table 5-3: Mycobacterial Infections M. tuberculosis, M. avium, M. kansasii, M. haemophilum, M. gordonae, M. genavense, M. xenopimalonoense, M. chelonei Table 5-4: Viruses Herpes simplex, Herpes zoster, Cytomegalovirus retinitis, Progressive multifocal leukoencephalopathy Table 5-5: Bacteria Streptococcus pneumoniae, Bartonella henselea/ quintana, Haemophilus influenzae, Nocardia asteroidePseudomonas aeruginosa, Rhodococcus equi, Salmonella, Staphylococcus aureus, Treponema pallidum Table 5-6: Treatment of Miscellaneous and Non-Infectious Disease Complications/Classified by Organ Syste Table 5-6A: Cardiac Table 5-6H: Gastrointestinal Table 5-6B: Pulmonary Table 5-6I: Hepatobiliary Table 5-6C: Renal Table 5-6J: Wasting Table 5-6D: Neurologic Table 5-6K: Pain Table 5-6E: Hematologic Table 5-6L: Psychiatric and Sleep Disorders Table 5-6F: Tumors Table 5-6M: Terminal Illness Table 5-6G: DermatologicTable 5-6: Continued - Treatment of Miscellaneous and Non-Infectious DiseaseComplications/Classified by Organ SystemCondition Treatment Comment5-6D. Neurologic
    • Nortriptyline 10 mg hs: Peripheral increase dose by 10 mg q 5 Other tricyclics commonly used: amitriptyline, desipramine, or imi days to maximum of 75 mg hsneuropathy or 10-20 mg PO tid Two large clinical trials failed to show benefit with tricyclics (ACTG Neurontin (gabapentin): JAMA 1998;280:1590). 300-1200 mg PO tid Capsaicin is usually not well tolerated. Ibuprofen 600-800 mg tid Mexiletine: appeared no better than placebo and was inferior to a Topical: Capsaicin-containing in ACTG 242. Experience with topical capsaicin ointment has also ointments (Zostrix, etc.) for disappointing. topical application; Lidocaine 20% to 30% ointment for One report of 2 patients suggests response to HAART (Lancet topical use 1998;352:1906). Lamotrigine (Lamictal) 25 mg bid increasing to 300 mg/day Clinical trials with lamotrigine show efficacy (Neurology 2000;54:2 over 6 weeks. Acupuncture: A controlled trial failed to show any benefit ( JAMA Alternatives: Phenytoin 1998;280:1590). 200-400 mg/day and carbamazepine 200-400 mg Nucleosides are commonly implicated, primarily d4T, ddI, and ddC PO bid order of risk is ddI/d4T/HU >ddI/d4T>d4T>ddI (AIDS 2000;14:273) drugs and drug combinations often require discontinuation or reduc Severe pain: Methadone, up prevent irreversible pain. to 200 mg qid, fentanynl patch 25-100 mg qod or morphine. Topiramate (Topamax) may be tried, but initial experience is not i Nerve growth factor was effective in some patients in ACTG 291, product is not commercially available. Myopathy Discontinue AZT x 3 weeks. AZT was a common cause of non-inflammatory myopathy when h Prednisone 40-60 mg/day (for were used, presumably due to mitochondrial toxicity. inflammatory) myopathy or IVIG 0.4 gm/kg x 5 days. Statins may cause myopathy. IVIG - EMG-biopsy confirmed.
    • Optimal HAART regimen for HAD is unknown. Good CSF suppreHIV-associated CSF HIV RNA levels is reported with NRTIs plus IDV, EFV, NFV, a Probable benefit from not for SQV/RTV (Adv Res and Ther 1998;8:10; AIDS 1998;12:357 dementia HAART. initial experience with HAART is that the incidence of HAD is reduc(HAD) (Neurology 1999;52:1640), and some patients with established HA Selegiline (Deprenyl) 5 mg cognitive and radiologic improvement by about 50% with HAART ( bid 2001;15:195), although the differences appear less striking than wi other HIV-related complications (AIDS 1999;13:1249). CSF levels of HIV RNA respond to HAART in some, but not all; re correlates with baseline CD4 cell count and plasma HIV RNA level The MAob inhibitor selegiline (Deprenyl) has shown improved me trials involving patients with HAD. Penetration across blood brain barrier is good for AZT, d4T, NVP and HU; it is modest for EFV, ddI, 3TC, and APV (J AIDS 1998;235 1998;12:537). Most of these drugs have been included in regimen elimination of detectable HIV RNA from CSF. Dementia staging: 0 Normal 0.5 Equivocal symptoms of cognitive or motor dysfunction 1 Evidence of intellectual or motor impairment but able to perform most aspects of work or ADL 2 Cannot work but can do self-care 3 Major intellectual or motor disability; cannot walk unassiste 4 Nearly vegetative Top of Page | Next page -- Treatment of Miscellaneous and Non-Infectious Disease Complicat HematologicCopyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rights reserved.* Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained in this site because noreference or service can take the place of medical training, education, and experience. Consumers are cautioned that this site is not intended to provideadvice about any specific medical condition they may have or treatment they may need and they are encouraged to call or see their physician or other hprovider promptly with any health related questions they may have.
    • Go to a Chapter Table of Contents Natural History and Classification Tests Disease Prevention Antiretroviral Therapy Management of Opp Infections Drugs: Guide to Information Systems Review HIV in CorrecV. Management of Opportunistic Infections and Other Complications of HIV Infection Opportunistic Infections Table 5-1: Fungal Pneumocystis carinii, Aspergillosis, Candidiasis, Cryptococcal meningitis, Cryptococcus without meningitis, HistoplasmoCoccidioidomycosis, Penicilliosis marneffei Table 5-2: Parasitic Infections Toxoplasma gondii, Cryptosporidiosis, Isosporidiosis, Microsporidiosis, Entamoeba histolytic Table 5-3: Mycobacterial Infections M. tuberculosis, M. avium, M. kansasii, M. haemophilum, M. gordonae, M. genavense, M. xenopimalonoense, M. chelonei Table 5-4: Viruses Herpes simplex, Herpes zoster, Cytomegalovirus retinitis, Progressive multifocal leukoencephalopathy Table 5-5: Bacteria Streptococcus pneumoniae, Bartonella henselea/ quintana, Haemophilus influenzae, Nocardia asteroidePseudomonas aeruginosa, Rhodococcus equi, Salmonella, Staphylococcus aureus, Treponema pallidum Table 5-6: Treatment of Miscellaneous and Non-Infectious Disease Complications/Classified by Organ Syste Table 5-6A: Cardiac Table 5-6H: Gastrointestinal Table 5-6B: Pulmonary Table 5-6I: Hepatobiliary Table 5-6C: Renal Table 5-6J: Wasting Table 5-6D: Neurologic Table 5-6K: Pain Table 5-6E: Hematologic Table 5-6L: Psychiatric and Sleep Disorders Table 5-6F: Tumors Table 5-6M: Terminal Illness Table 5-6G: DermatologicTable 5-6: Continued - Treatment of Miscellaneous and Non-InfectiousDisease Complications/Classified by Organ SystemCondition Treatment Comment5-6E: HematologicIdiopathic HAART Anecdotal experience with HAART is good (Nthrombocytopenic 1999;341:1239; Clin Infect Dis 2000;30:504)purpura (ITP) Discontinue any drugs potentially responsibleAsymptomatic Note: Standard treatments (prednisone, IVIG, splenectomy, etc.) show response rates of 40% main problem is lack of a durable response (see Dis 1995;21:415). Response to AZT may be dose-related; usuall within 2 to 4 weeks. Utility of other nucleoside a unknown. HAART was associated with a mean platelet count of 38,000/mm3 (Clin Infect Dis 20Severe Packed red cell/platelet transfusions plushemorrhage prednisone 60-100 mg/day or IVIG 1 g/kg on days 1, 2, 14, and then q 2 to 3 weeks
    • Persistent AZT 600-1,200 mg/day (in combination Usual AZT dose is 500-600 mg/day; doses ofsymptomatic ITP regimen) and HAART mg/day are reserved for non-responders. Respo noted in 2 to 4 weeks. Initial results with HAART Discontinue drugs potentially responsible and good response (N Engl J Med 1999;341:1239). avoid NSAIDS Prednisone may be complicated by opportunis Prednisone 30-60 mg/day with rapid taper to infections, esp. thrush and herpes, and decreas 5-10 mg/day count; only 10% to 20% have persistent respon IVIG is highly effective in raising platelet count days, but is very expensive and median duration response is only 3 weeks. IVIG 400 mg/kg days 1, 2, and 14, then q 2 to WinRho is an alternative to IVIG in Rh positive 3 weeks or WinRho 25-50 µg/kg IV over 3 to 5 patients. Advantages are 3 to 5 minute infusions minutes, repeat at day 3 to 4 as necessary; safety profile, and low cost (Blood 1991;77:1884 may need maintenance therapy at 3- to 4-week intervals using 6-25 µg/kg Experience with splenectomy is variable: dura response is variable. Some claim risk of HIV pro increased (Lancet 1987;2:342), and others claim long-term results (Arch Surg 1989;124:625). Experimental or limited experience with all fou Splenectomy Splenic irradiation, danazol, vincristine, interferonAnemia Treatment based on cause HIV: HAART Decreased production: Marrow infiltrating tum AZT: Discontinue AZT or reduce dose, and/or (lymphoma, KS), infection (MAC, TB, CMV, parv add EPO B19, fungal-esp. histoplasmosis), drugs (AZT, amphotericin, ganciclovir, HU, pyrimethamine, i anemia of chronic disease, deficiency states (Fe B 12), HIV inhibition of precursors (Clin Infect Dis 2000;30:504). Increased destruction (hemolysis) TTP, drugs (sulfonamides, dapsone, or primaquine plus G6 deficiency). Parvovirus B19: IVIG Parvovirus B19 - Marrow shows giant pronorm with clumped basophilic chromatin and clear cy vacuoles - diagnosis by in situ hybridization or P Guidelines for erythropoietin therapy
    • Neutropenia G-CSF (Neupogen) or GM-CSF (Prokine) Drugs associated with neutropenia: AZT and g 1-10 µg/kg/day SC; usual initial dose for less common - 3TC, ddI, d4T, foscarnet, ribaviri G-CSF is 5 µg/kg/day with increases of 1 amphotericin, sulfonamides, pyrimethamine, pe µg/kg/day at 5- to 7-day intervals to maintain antineoplastic agents, and interferon. Discontin ANC at 1000-2000/mm3; usual maintenance implicated drug(s) when feasible. dose is 300 mcg given 3 to 7x/week HIV may cause neutropenia by inhibition of pre HAART (Clin Infect Dis 2000;30:504). Reported risk of infectious complications is var largest analysis showed higher risk for hospitali ANC <500 (Arch Intern Med 1997; 157: 1825). G-CSF therapy: Monitor with CBC and diff 2x/w titrate up by 1 µg/kg/day or: reduce dose 50% p maintenance to keep ANC >1000-2000/mL. Effi G-CSF is established for elevating neutrophil co J Med 1987;317:593). Concern with GM-CSF is possible increased H replication, but this is not substantiated in >3 tri recommendations are identical to those given fo but starting dose is 5 µg/kg/day (AIDS 1996;12:Thrombotic Prednisone 60-100 mg/day plusthrombocytopenic plasmapheresispurpuraTop of Page | Next page -- Treatment of Miscellaneous and Non-Infectious Disease ComplicationsCopyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rights reserved.* Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained in this site because noreference or service can take the place of medical training, education, and experience. Consumers are cautioned that this site is not intended to provideadvice about any specific medical condition they may have or treatment they may need and they are encouraged to call or see their physician or other hprovider promptly with any health related questions they may have.
    • Go to a Chapter Table of Contents Natural History and Classification Tests Disease Prevention Antiretroviral Therapy Management of Opp Infections Drugs: Guide to Information Systems Review HIV in CorrecV. Management of Opportunistic Infections and Other Complications of HIV Infection Opportunistic Infections Table 5-1: Fungal Pneumocystis carinii, Aspergillosis, Candidiasis, Cryptococcal meningitis, Cryptococcus without meningitis, HistoplasmoCoccidioidomycosis, Penicilliosis marneffei Table 5-2: Parasitic Infections Toxoplasma gondii, Cryptosporidiosis, Isosporidiosis, Microsporidiosis, Entamoeba histolytic Table 5-3: Mycobacterial Infections M. tuberculosis, M. avium, M. kansasii, M. haemophilum, M. gordonae, M. genavense, M. xenopimalonoense, M. chelonei Table 5-4: Viruses Herpes simplex, Herpes zoster, Cytomegalovirus retinitis, Progressive multifocal leukoencephalopathy Table 5-5: Bacteria Streptococcus pneumoniae, Bartonella henselea/ quintana, Haemophilus influenzae, Nocardia asteroidePseudomonas aeruginosa, Rhodococcus equi, Salmonella, Staphylococcus aureus, Treponema pallidum Table 5-6: Treatment of Miscellaneous and Non-Infectious Disease Complications/Classified by Organ Syste Table 5-6A: Cardiac Table 5-6H: Gastrointestinal Table 5-6B: Pulmonary Table 5-6I: Hepatobiliary Table 5-6C: Renal Table 5-6J: Wasting Table 5-6D: Neurologic Table 5-6K: Pain Table 5-6E: Hematologic Table 5-6L: Psychiatric and Sleep Disorders Table 5-6F: Tumors Table 5-6M: Terminal Illness Table 5-6G: DermatologicTable 5-6: Continued - Treatment of Miscellaneous and Non-InfectiousDisease Complications/Classified by Organ SystemCondition Treatment Comment5-6F: Tumors (J AIDS 1999;21:566)KS General KS is caused by HHV-8 - risks for malignant transformation infection, low CD4 cell count, and high viral load (J Infect DisACTG 181:1940).classification (seeMayo Clin Proc KS generally responds to HAART; the CD4 cell count respo1995;70:869) best predictor (AIDS 2000;14:987; AIDS 2000;14:971).See comments Good prognosis: Lesions confined to skin and/or nodes; CD4 cell count >150, no "B symptoms" Poor prognosis: Lesion-associated edema, severe oral KS, visceral KS CD4 cell count <150, hx of OI, or "B symptoms"
    • Local Therapy: Restrict to few lesions that are small. Topical liquid nitrogen Restrict to few lesions that may be larger (>1 cm). Intralesional vinblastine (0.01-0.002 mg/lesion) q 2 weeks x 3 Skin - well tolerated; oral lesion - mucositis common. Best w localized lesions Laser, radiation, or vinblastine injection preferred for oral les Radiation (low dose, eg 400 rads/week x 6 weeks) Laser Systemic Therapy: Liposomal anthracyclines are alternatives to ABV chemothe Liposomal daunorubicin (DaunoXome) show comparable clinical efficacy and reduced toxicity (AIDS 40-60 mg/m 2 IV q 2 weeks or liposomal 1996;10:515). doxorubicin (Doxil) 10-20 mg/m 2 Systemic therapy is preferred for patients with widespread s involvement (>25 lesions), extensive cutaneous KS that is Taxol 100-135 mg/m2 q 2 to 3 nonresponsive to local treatment, extensive edema, and/or sy weeks visceral organ involvement (especially lung KS)/(Lancet 1995 Adriamycin, bleomycin, and either Taxol is FDA-approved for KS. vincristine or vinblastine (ABV) Vincristine/vinblastine Bleomycin/vinca alkaloids Alpha interferon (18-36 million IU/day) IM or SC x 10 to 12 weeks then 18 million units/day - 36 million units 3x/week Experimental: Foscarnet (Scand J HHV-8 is susceptible to foscarnet, ganciclovir, and cidofovir Infect Dis 1994;26:749); Invest 1997;99:2082); role of antiretroviral agents in therapy i thalidomide (Clin Infect Dis A retrospective analysis of patients with CMV disease showed 1996;23:501); HAART; therapy was associated with a significant delay in progression intralesional B-human chorionic AIDS 1999;20:34); oral or IV ganciclovir given for CMV retinit gonadotropin 2000 U per lesion; significantly reduced the frequency of KS (N Engl J Med 1999 retinoic acid isomers oral or IV ganciclovir given for CMV retinitis significantly redu frequency of KS (N Engl J Med 1999;340:1063).Non-Hodgkins Low-dose chemotherapy is as effective as standard dose (Alymphoma (NHL) methotrexate 200 mg/m2 , bleomycin 4 U/m2 , doxorubicin 25 m EPOCH: etoposide, vincristine and doxorubicin by 96-hour cyclophosphamide 300 mg/m2 , vincristine 1.4 mg/m2 , dexame continuous infusion + mg/m2 /GM-CSF 5 mcg/kg for >4 cycles. The AIDS Malignanc cyclophosphamide + prednisone Consortium recommend low-dose CHOP or low-dose mBACO bolus vincristine + dexamethasone on this ACTG (N Engl J Med 1997;336:1641). However, the m results with CHOP and BACOD have been disappointing; mo promising results are reported with EPOCH in non-HIV-infecte Regimens containing (JAMA 2001;285:1882). methotrexate, bleomycin, doxorubicin, cyclophosphamide, adriamycin, vincristine, and corticosteroids ± cranial radiation; standard regimens are CHOP and mBACOD/GM-CSF
    • Primary CNS CNS lymphoma - cranial radiation Many respond to radiation (J Neurosurg 1990;73:206), but alymphoma plus high-dose corticosteroids + survival is only 2 to 5 months (Cancer 1994;73:2570). chemotherapy.Cattlemans Case report of response to interferon-alfa 5x10 6 units 3x wedisease Infect Dis 2000;31:602). Top of Page | Next page -- Treatment of Miscellaneous and Non-Infectious Disease Complicat DermatologicCopyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rights reserved.* Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained in this site because noreference or service can take the place of medical training, education, and experience. Consumers are cautioned that this site is not intended to provideadvice about any specific medical condition they may have or treatment they may need and they are encouraged to call or see their physician or other hprovider promptly with any health related questions they may have.
    • Go to a Chapter Table of Contents Natural History and Classification Tests Disease Prevention Antiretroviral Therapy Management of Opp Infections Drugs: Guide to Information Systems Review HIV in CorrecV. Management of Opportunistic Infections and Other Complications of HIV Infection Opportunistic Infections Table 5-1: Fungal Pneumocystis carinii, Aspergillosis, Candidiasis, Cryptococcal meningitis, Cryptococcus without meningitis, HistoplasmoCoccidioidomycosis, Penicilliosis marneffei Table 5-2: Parasitic Infections Toxoplasma gondii, Cryptosporidiosis, Isosporidiosis, Microsporidiosis, Entamoeba histolytic Table 5-3: Mycobacterial Infections M. tuberculosis, M. avium, M. kansasii, M. haemophilum, M. gordonae, M. genavense, M. xenopimalonoense, M. chelonei Table 5-4: Viruses Herpes simplex, Herpes zoster, Cytomegalovirus retinitis, Progressive multifocal leukoencephalopathy Table 5-5: Bacteria Streptococcus pneumoniae, Bartonella henselea/ quintana, Haemophilus influenzae, Nocardia asteroidePseudomonas aeruginosa, Rhodococcus equi, Salmonella, Staphylococcus aureus, Treponema pallidum Table 5-6: Treatment of Miscellaneous and Non-Infectious Disease Complications/Classified by Organ Syste Table 5-6A: Cardiac Table 5-6H: Gastrointestinal Table 5-6B: Pulmonary Table 5-6I: Hepatobiliary Table 5-6C: Renal Table 5-6J: Wasting Table 5-6D: Neurologic Table 5-6K: Pain Table 5-6E: Hematologic Table 5-6L: Psychiatric and Sleep Disorders Table 5-6F: Tumors Table 5-6M: Terminal Illness Table 5-6G: DermatologicTable 5-6: Continued - Treatment of Miscellaneous and Non-Infectious DiseaseComplications/Classified by Organ SystemCondition Treatment Comment5-6G: Dermatologic Complications Bacillary Erythromycin 500 mg PO qid or doxycycline 200 See Bartonellaangiomatosis mg/day x >3 months Dermatophytic Skin - Topical miconazole or clotrimazole. Ointments (miconazole and clotrimazole) afungi Refractory cases: ketoconazole 200 mg/day PO x 1 over-the-counter. to 3 months or itraconazole 100 mg/day Nails - Griseofulvin 660 mg/day x 6 to 15 months or itraconazole 200 mg bid x 1 week/month x 2 (fingernails) or 3 to 4 months (toenails) or terbinafine 250 mg/day x 6 weeks (fingernails) or 12 weeks (toenails)
    • Eosinophilic Astemizole 10 mg qd/topical steroids Oral agents that have limited experience: ifolliculitis 200 mg/day x 14 to 21 days, dapsone 100-2 isotretinoin 1 mg/kg/day or metronidazole ( Ultraviolet light Dermatol 1995;131:1047; Arch Dermatol 1995;131:359). Efficacy of UV light established (N Engl J M 1988;318:1183). Antihistamine Only sedating antihistamines are useful Molluscum Cryotherapy; electrosurgery; curettage, topical Cidofovir appears to work when given IV ocontagiosum cantharidin or cidofovir (Lancet 1999;353:2042). Topical formulation commercially available. HAART Scabies Permethrin cream 5% x 12 hours; repeat 3 to 7 Must apply permethrin cream to all skin su days later Lindane should not be applied to the face. Topical lindane Ivermectin 200 mg x 1 Seborrhea Skin - Steroid cream (hydrocortisone 1%) + Use topical hydrocortisone (2.5%) until les precipitated sulfur (desonide cream) or topical resolve, then 1% for maintenance. ketoconazole applied bid Scalp - Shampoos containing selenium sulfide, zinc pyrithione, salicylic acid, or coal tar applied 1x/day or ketoconazole shampoo 2x/week. Staphylococcal Cephalexin or dicloxacillin 500 mg PO qid x 7 to 21 Add RIF 600 mg/day x 7 days if severe orfolliculitis days Recurrent disease: chronic antibiotic (clind mg/day or TMP-SMX 1 DS/day) and/or nasa bid x 2 weeks every 3 months.
    • Top of Page | Next page -- Treatment of Miscellaneous and Non-Infectious Disease Complicat Gastrointestinal/Pancreatitis/Oral/Esophagus/Diarrhea/HepatobiliaryCopyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rights reserved.* Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained in this site because noreference or service can take the place of medical training, education, and experience. Consumers are cautioned that this site is not intended to provideadvice about any specific medical condition they may have or treatment they may need and they are encouraged to call or see their physician or other hprovider promptly with any health related questions they may have.
    • Go to a Chapter Table of Contents Natural History and Classification Tests Disease Prevention Antiretroviral Therapy Management of Opp Infections Drugs: Guide to Information Systems Review HIV in CorrecV. Management of Opportunistic Infections and Other Complications of HIV Infection Opportunistic Infections Table 5-1: Fungal Pneumocystis carinii, Aspergillosis, Candidiasis, Cryptococcal meningitis, Cryptococcus without meningitis, HistoplasmoCoccidioidomycosis, Penicilliosis marneffei Table 5-2: Parasitic Infections Toxoplasma gondii, Cryptosporidiosis, Isosporidiosis, Microsporidiosis, Entamoeba histolytic Table 5-3: Mycobacterial Infections M. tuberculosis, M. avium, M. kansasii, M. haemophilum, M. gordonae, M. genavense, M. xenopimalonoense, M. chelonei Table 5-4: Viruses Herpes simplex, Herpes zoster, Cytomegalovirus retinitis, Progressive multifocal leukoencephalopathy Table 5-5: Bacteria Streptococcus pneumoniae, Bartonella henselea/ quintana, Haemophilus influenzae, Nocardia asteroidePseudomonas aeruginosa, Rhodococcus equi, Salmonella, Staphylococcus aureus, Treponema pallidum Table 5-6: Treatment of Miscellaneous and Non-Infectious Disease Complications/Classified by Organ Syste Table 5-6A: Cardiac Table 5-6H: Gastrointestinal Table 5-6B: Pulmonary Table 5-6I: Hepatobiliary Table 5-6C: Renal Table 5-6J: Wasting Table 5-6D: Neurologic Table 5-6K: Pain Table 5-6E: Hematologic Table 5-6L: Psychiatric and Sleep Disorders Table 5-6F: Tumors Table 5-6M: Terminal Illness Table 5-6G: DermatologicTable 5-6: Continued - Treatment of Miscellaneous and Non-Infectious DiseaseComplications/Classified by Organ SystemCondition Treatment Comment5-6H: Gastrointestinal Anorexia Megace 400-800 mg qd Weight gain is mostly fat. May lower testos levels, leading to muscle wasting. Synthetic THC, an active ingredient in marij Dronabinol (Marinol) 2.5 mg PO bid Weight gain is mostly fat. Rule out reversible causes: depression, gastrointestinal disease, medication side effe hypogonadism, lactic acidosis, etc.
    • Nausea/vomiting Compazine 5-10 mg PO q6h-q8h; Tigan 250 Phenothiazines (Compazine, etc.), haloperi mg PO q6h-q8h; Dramamine 50 mg PO (Haldol), trimethobenzamide (Tigan)and met q6h-q8h; Ativan 0.025-0.05 mg/kg IV or IM; (Reglan) may cause dystonia. haloperidol 1-5 mg bid PO or IM; ondansetron (Zofran) 0.2 mg/kg IV or IM; Dronabinol 2.5-5 Rule out medication-related nausea mg PO bid Ondansertron efficacy established only for chemotherapy; cost is $16.66/4 mg Pancreatitis: Drugassociated D/C implicated drug Most common - ddI, possible enhanced rate is combined with HU. Others: pentamidine, sulfonamides, corticost PIs (secondary to drug-induced hypertriglyce Possible causes: INH, 3TC, (reported in ped patients only) RIF, erythromycin, paromomyc and other NRTIs as a component of mitochon toxicity. Pancreatitis: Treat implicated agent CMV; less common: MAC, TB, cryptosporidInfection (OIs) toxoplasmosis. Pancreatitis: Treat implicated agent ETOH, hypertriglyceridemia, ERCP, morbidGeneral Causes cholelithiasisOral Mouth rinses with Miles solution, Miles solution - 60 mg hydrocortisone, 20 c Aphthous ulcers dexamethasone (0.5 mg/mL), Dyclone (10%), mycostatin, 2 g tetracycline, and 120 cc visco Benadryl or viscous Lidocaine (2%) Lidocaine. Topical fluocinonide (Lidex) 0.05% ointment Lesions are considered major or minor on b mixed 1:1 with Orobase size, depth and duration. Major lesions are > usually painful, usually persistent, and often Decadron 0.5 mg/5 mL elixir mouth rinse 1-3x/day (multiple lesions) Thalidomide is experimental for this indicati there are strict restrictions for use, but initial Thalidomide 200 mg/day PO x 4 to 6 weeks, good (N Engl J Med 1997;337:1086; Clin Infe then 100 mg 2x/week 1995;20:250; J Infect Dis 1999;180:61). Colchicine 1.5 mg/day (J Am Acad Derm 1994;31:459) Prednisone 40 mg/day PO x 1 to 2 weeks, then taper (severe or refractory cases) Oral hairy Acyclovir 800 mg PO 5x/day x 2 to 3 weeks,leukoplakia then 1.2 - 2 g/day Most lesions are asymptomatic and do not treatment; relapses are common when acyclo discontinued. Tretinoin (Retin A) .025% to 0.05% solution applied 2 to 3x/day Famciclovir, valacyclovir, foscarnet, and ga should be as effective as acyclovir
    • Salivary gland Xerostomia: sugarless gum and artificial CT scan will distinguish cystic and solid lesenlargement saliva; pilocarpine for refractory cases (Laryngoscope 1988;98:772). Biopsy if malig suspected. (Most are benign cystic lesions.) Painful or cosmetically disfiguring cystic lesions: needle aspiration Fine needle aspirate permits microbiologic and decompression. Curettage and debridement of involved Four phases: gingival erythema, necrotizingGingivitis/periodontitis tissue/topical antiseptic such as necrotizing periodontitis, and necrotizing stom povidine-iodine solution and chlorhexidine Intern Med 1996;125:485). (Peridex) mouth rinses Usual presenting complaints are oral pain a Metronidazole 250 mg tid or 500 mg PO bid bleeding. x 7 to 14 days or clindamycin 300 mg tid x 7 to 14 days in selected casesEsophagitits Fluconazole 200 mg/day PO x 14 to 21 days Alternatives: ketoconazole (less effective) ( Candida Med 1992;117:655); itraconazole (some fluconazole-resistant Candida sp. are sensiti (Antimicrob Agents Chemother 1994;38:1530 amphotericin B systemically for refractory ca CMV Ganciclovir 5 mg/kg IV bid x 14 to 21 days or For patients with complete response, disco foscarnet 60 mg/kg/IV q8h x 14 to 21 days induction therapy and use maintenance only relapse. Herpes simplex Acyclovir 400-800 mg PO 5x/day or 5 mg/kg Relatively rare cause of esophagitis IV tid x 7 to 10 days or valacyclovir or famciclovir Aphthous ulcer Prednisone 40 mg/day PO x 2 weeks, then Thalidomide is considered experimental, an slow taper strict restrictions for use in women, but effica documented (BMJ 1989;298:432; N Engl J M Intralesional steroids 1997;337:1086; AIDS Res Human Retrovirus 1997;13:301; Clin Infect Dis 1995;20:250; J I 1999;180:61). Thalidomide 200 mg PO/day
    • Diarrhea See comments Note: Diarrhea does not appear to reduce bioavailability of oral drugs, with the exceptio atovaquone. E. coli: Travelers diarrhea - ciprofloxacin 50 Specific microbial bid x 3 day TMP-SMX 1DS bid x 3 days; E. cagent (enterohemorrhagic E. coli): antibiotic treatm (see Clin Infect Dis contraindicated2001;32:331) C. jejuni: Erythromycin 500 mg PO bid x 5 d C. difficile Metronidazole 500 mg tid x 10 da Salmonella: Ciprofloxacin 500 mg PO bid x TMP-SMX 1 DS bid x >14 days (if sensitive) Cefotaxime 4-8 gm/day IV x 14 days Shigella: TMP-SMX 1 DS bid x 3 days Ciprofloxacin 500 mg PO bid x 3 days Aeromonas: TMP-SMX 1 DS bid x 3 days Ciprofloxacin 500 mg PO bid x 3 days E. histolytica: Metronidazole 750 IV or PO t days + paromomycin 500 mg PO tid x 7 days Giardia: Metronidazole 250-750 mg PO tid days Cryptosporidia, isospora, microsporidia: see organism Bacterial overgrowth Doxycycline (100 mg PO bid), metronidazole Diagnosis requires quantitative culture of s (500-750 mg PO bid) or aspirate or hydrogen breath test. amoxicillin-clavulanate (500 mg PO qid) Protease inhibitor All are sold over-the-counter at $4 to $10/m (Clin Infect Dis pancreatic enzymes. Psyllium 1 tsp qd-bid or 2 bars qd-bid2000;30:908) Loperamide 4 mg then 2 mg with each loose stool up to 16/day Oat bran 1500 mg bid Calcium 500 mg bid Pancreatic enzymes 1 to 2 tabs with meals
    • Symptomatic Diphenoxylate/atropine Utility of bismuth salts (Pepto-Bismol), indotreatment (Lomotil)/loperamide/paregoric, etc. and Octreotide not known. Diet modification: low fat, no caffeine, no milk PIs commonly cause diarrhea, especially N or milk products presumed mechanism is secretory (7th CRO Francisco, Calif., February 2000, Abstract 625-6I: Hepatobiliary Papillary stenosis ERCP with sphincterotomy Presentation: right upper quadrant pain, LF cholestasis; diagnosis is established with ER Sensitivity of ultrasound is 75% to 95%. Cholangiopathy Ursodeoxycholic acid 300 mg PO tidwithout Usual causes are cryptosporidium (most co (experience limited) papillary stenosis microsporidia, CMV, and cyclospora. About 2 idiopathic. Treatment directed against microbial pathog unsuccessful for cholangitis. Isolated bile duct Endoscopic stentingstructure Improvement with ursodeoxycholic acid is r small number of patients (Am J Med 1997;10 Hepatitis A vaccine if HAV seronegative Diagnostic evaluation: see Testing for Hep Hepatitis C (Clin Infect Dis HCV therapy: alpha interferon, 3 million units Indications to treat: The main indication is b2000;31:154) SC 3x/week plus ribavirin 1000-1200 mg/day evidence of bridging fibrosis or moderate infl PO x 24 weeks for genotype 2 & 3 or 48 and necrosis. HCV RNA levels and ALT leve weeks for genotype 1 (Lancet adequately predict prognosis. 1999;351:1426). Ribavirin works well in HIV-infected patients Peginterferon alfa 2 (Pegasys, Roche) or alfa causes more anemia (Clin Infect Dis 2000;31 2 b (Peg-Intron, Schering) 1.0 to 1.2 mg/kg/week; both should be combined with ribavirin 10.6 mg/kg/day x 48 weeks Factors that promote HCV progression are co-infection and alcohol ingestion of >50 g E (Clin Infect Dis 1999;29:75). HCV has disput HIV progression. All antiretroviral drugs are potentially hepat a frequency of 3% to 12% without hepatitis; r higher with chronic HCV (JAMA 2000;283:74 NVP are the most hepatotoxic. Peginterferon has a longer half-life than inte permitting once-weekly adminstration. Comp trials with peginterferon (180 µg/wekk SC) vs alfa 2a (3 to 6 million units SC 3x/week) x 48 patients with chronic HCV showed peginterfe superior in terms of virologic response and li tests (ALT) at 72 weeks (N Engl J Med 2000 N Engl J Med 2000;343:1673). Peginterferon monotherapy results are inferior to interferon
    • Hepatitis B 3TC 150 mg bid (HIV) or 100 mg/day (HBV) Efficacy of 3TC is well established, and it is FDA-approved for this indication (N Engl J M Interferon 30-35 mil units/week x 4 months 1998;339:61). HBV control may be achieved with HAART no agents with anti-HBV agents (N Engl J Me 1999;340:1765). 3TC + famciclovir (500 mg bid or tid) is som used to decrease 3TC resistance and is cons experimental.Top of Page | Next page -- Treatment of Miscellaneous and Non-Infectious Disease ComplicationsCopyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rights reserved.* Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained in this site because noreference or service can take the place of medical training, education, and experience. Consumers are cautioned that this site is not intended to provideadvice about any specific medical condition they may have or treatment they may need and they are encouraged to call or see their physician or other hprovider promptly with any health related questions they may have.
    • Go to a Chapter Table of Contents Natural History and Classification Tests Disease Prevention Antiretroviral Therapy Management of Opp Infections Drugs: Guide to Information Systems Review HIV in CorrecV. Management of Opportunistic Infections in Patients with HIV InfectionOpportunistic Infections Table 5-1: Fungal Pneumocystis carinii, Aspergillosis, Candidiasis, Cryptococcal meningitis, Cryptococcus without meningitis, HistoplasmoCoccidioidomycosis, Penicilliosis marneffei Table 5-2: Parasitic Infections Toxoplasma gondii, Cryptosporidiosis, Isosporidiosis, Microsporidiosis, Entamoeba histolytic Table 5-3: Mycobacterial Infections M. tuberculosis, M. avium, M. kansasii, M. haemophilum, M. gordonae, M. genavense, M. xenopimalonoense, M. chelonei Table 5-4: Viruses Herpes simplex, Herpes zoster, Cytomegalovirus retinitis, Progressive multifocal leukoencephalopathy Table 5-5: Bacteria Streptococcus pneumoniae, Bartonella henselea/ quintana, Haemophilus influenzae, Nocardia asteroidePseudomonas aeruginosa, Rhodococcus equi, Salmonella, Staphylococcus aureus, Treponema pallidum Table 5-6: Treatment of Miscellaneous and Non-Infectious Disease Complications/Classified by Organ Syste Table 5-6A: Cardiac Table 5-6H: Gastrointestinal Table 5-6B: Pulmonary Table 5-6I: Hepatobiliary Table 5-6C: Renal Table 5-6J: Wasting Table 5-6D: Neurologic Table 5-6K: Pain Table 5-6E: Hematologic Table 5-6L: Psychiatric and Sleep Disorders Table 5-6F: Tumors Table 5-6M: Terminal Illness Table 5-6G: DermatologicTable 5-6: Continued - Treatment of Miscellaneous and Non-Infectious DiseaseComplications/Classified by Organ SystemCondition Treatment Comment5-6J: Wasting
    • (see Enteral feedingsChapter 7) Polymeric formulas: Nonprescription about $1.50/can; 10 Polymeric formulas: Ensure, Sustecal, required for total caloric needs. Usually not effective in wa Enrich, etc. Elemental diet for severe malabsorption states; often due Elemental formulas: Vivonex TEN cryptosporidia, microsporidia, or severe CMV infection. Parenteral hyperalimentation: Rarely indicated except for devastating diarrhea due to cryptosporidiosis. Caloric supplements in patients with stable weight do not weight gain (J AIDS 1999;22:253). Appetite Stimulants Usually used in conjunction with anabolic steroids. Megestrol (Megace) 400-800 mg/day Dronabinol (Marinol) 2.5 mg PO bid Recommended only if weight loss is due to reduced intak Megace: Weight gain is mostly fat. May lower testosteron leading to impotence. Dronabinol: Weight gain is mostly fat. Anabolic steroids High anabolic effect and low androgenic effect. Most wei Nandrolone 100-200 mg IM q 2 weeks lean body mass. (men) 25-100 mg IM q 2 weeks (women) Safety of nandrolone in women is established by experien Oxandrolone 20 mg/day PO (men and treatment of post-menopausal osteoporosis. women) Oxandralone shows highest weight gain of all treatments. Oxymetholone (Anadrol-50): 100-150 mg/day PO, up to 300 mg/day Resistance testing recommended for patients taking ana steroids. Testosterone Indicated for hypogonadism with or without wasting. Androderm patch 5 mg/day Numerous studies show improved quality of life for hypog Testoderm TTS patch 5 mg/day men given testosterone (Arch Gen Psychiatry 2000;57:141 AndroGel topical 5 g/day Testosterone is available for oral, injectable, or transderm Oral compounds have been associated with liver toxicity a Testerone enathate or testerone cypionate 200-400 mg be avoided; IM injections consist of an ester in oil that exte IM q 2 weeks or 100-200 mg IM by self injection. Often to permit weekly or biweekly administration. start with 400 mg IM q 2 weeks and then decrease to replacement dose of 200 mg IM q 2 weeks. Serum testosterone levels <450 ng/dL are associated wit decreased libido. Drugs associated with decreased testost levels are megesterol, ketoconazole, and cimetidine. High androgenic and anabolic effect with: improved mood libido, energy, appetite, and lean body mass.
    • Serum testosterone levels <450 ng/dL are associated wit decreased libido. Drugs associated with decreased testost levels are megesterol, ketoconazole, and cimetidine. High androgenic and anabolic effect with: improved mood libido, energy, appetite, and lean body mass. About 50% of men with AIDS have hypogonadism (J Clin 1996;81:4051). Testosterone is most effective in these cas J Med 1999;340:1740). Optimal results are achieved when testosterone is combined with a resistance exercise progra 2000;283:763). AndroGel is a non-patch formulation that permits dose ad (Med Letter 2000;42:49). An NIH-sponsored study showed that eugonadol men wit obtained increased lean body mass with testosterone (200 IM) and progressive resistance training (Ann Intern Med 2000;133:348). Resistance exercise: 20 to 120 Effective in increasing lean body mass; preliminary results minutes/day 3x/week efficacy reversing the fat accumulation ascribed to PIs (AID 1999;13:1373). Cytokine suppression Experimental; interest is based on possible suppression Thalidomide (Thalomid) 100 mg/day PO, efficacy established for tuberculosis and shows promise in up to 300 mg/day. unpublished controlled trials for AIDS patients. Pentoxifylline (Trentol) Pentoxifylline: Usually not effective. Growth hormone (Serostim) 6 mg SC qd x Most weight gain is lean body mass. 12 weeks Disadvantages are high cost ($1750/week), need for injec side effects. Alternative regimen is for administration for 2 weeks at th OIs (AIDS 1999;13:1195). May reverse fat accumulation seen with PIs, but may exa atrophy (AIDS 1999;13:2099). Top of Page | Next page -- Treatment of Miscellaneous and Non-Infectious Disease ComplicationCopyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rights reserved.* Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained in this site because noreference or service can take the place of medical training, education, and experience. Consumers are cautioned that this site is not intended to provideadvice about any specific medical condition they may have or treatment they may need and they are encouraged to call or see their physician or other hprovider promptly with any health related questions they may have.
    • Go to a Chapter Table of Contents Natural History and Classification Tests Disease Prevention Antiretroviral Therapy Management of Opp Infections Drugs: Guide to Information Systems Review HIV in CorrecV. Management of Opportunistic Infections in Patients with HIV Infection Opportunistic Infections Table 5-1: Fungal Pneumocystis carinii, Aspergillosis, Candidiasis, Cryptococcal meningitis, Cryptococcus without meningitis, HistoplasmoCoccidioidomycosis, Penicilliosis marneffei Table 5-2: Parasitic Infections Toxoplasma gondii, Cryptosporidiosis, Isosporidiosis, Microsporidiosis, Entamoeba histolytic Table 5-3: Mycobacterial Infections M. tuberculosis, M. avium, M. kansasii, M. haemophilum, M. gordonae, M. genavense, M. xenopimalonoense, M. chelonei Table 5-4: Viruses Herpes simplex, Herpes zoster, Cytomegalovirus retinitis, Progressive multifocal leukoencephalopathy Table 5-5: Bacteria Streptococcus pneumoniae, Bartonella henselea/ quintana, Haemophilus influenzae, Nocardia asteroidePseudomonas aeruginosa, Rhodococcus equi, Salmonella, Staphylococcus aureus, Treponema pallidum Table 5-6: Treatment of Miscellaneous and Non-Infectious Disease Complications/Classified by Organ Syste Table 5-6A: Cardiac Table 5-6H: Gastrointestinal Table 5-6B: Pulmonary Table 5-6I: Hepatobiliary Table 5-6C: Renal Table 5-6J: Wasting Table 5-6D: Neurologic Table 5-6K: Pain Table 5-6E: Hematologic Table 5-6L: Psychiatric and Sleep Disorders Table 5-6F: Tumors Table 5-6M: Terminal Illness Table 5-6G: DermatologicTable 5-6: Continued - Treatment of Miscellaneous and Non-Infectious DiseaseComplications/Classified by Organ SystemCondition Treatment Comment5-6K: Pain
    • ASA, acetaminophen, Severe pain is best relieved with opioids.(see Med Let 325-750 mg q4h1993;35:1-6) Chronic pain is best treated with nonopioid initially (ASA, acetam NSAIDS (Motrin 200-400 mg ibuprofen, nortriptyline). q6h; Naprosyn 230-375 mg(see "pain q6h-q8h) Dependence liability for opioids.control") Codeine 30-60 mg q4h-q6h Side effects of opiods: sedation, constipation, respiratory depres PO, SC, or IM nausea, and vomiting. Meperidine 50-150 mg Oral codeine, propoxyphene (Darvon) and pentazocine in usual q3h-q4h PO, SC, IM, IV no more effective than ASA. Morphine, dilaudid, methadone, levo fentanyl, and large doses of oxycodone are needed for severe pa Methadone 2.5-10.0 mg q6h-q8h PO, 10 mg IM Morphine and other full agonists have no limit on analgesic effec except for the limit ascribed to side effects. Dilaudid 2-8 mg q4h-q8h PO or rectal; 20-60 mg PO MS Contin 15-70 mg PO bid Nortriptyline 25-75 mg qd hs Fentanyl patch 25-100 mcg/hour Ultram (tramadol) 50-100 mg q4h-q6h, up to 400 mg/day Top of Page | Next page -- Treatment of Miscellaneous and Non-Infectious Disease Complicat Psychiatric and Sleep Disorders/Terminal IllnessCopyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rights reserved.* Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained in this site because noreference or service can take the place of medical training, education, and experience. Consumers are cautioned that this site is not intended to provideadvice about any specific medical condition they may have or treatment they may need and they are encouraged to call or see their physician or other hprovider promptly with any health related questions they may have.
    • Go to a Chapter Table of Contents Natural History and Classification Tests Disease Prevention Antiretroviral Therapy Management of Opp Infections Drugs: Guide to Information Systems Review HIV in CorrecV. Management of Opportunistic Infections in Patients with HIV Infection Opportunistic Infections Table 5-1: Fungal Pneumocystis carinii, Aspergillosis, Candidiasis, Cryptococcal meningitis, Cryptococcus without meningitis, HistoplasmoCoccidioidomycosis, Penicilliosis marneffei Table 5-2: Parasitic Infections Toxoplasma gondii, Cryptosporidiosis, Isosporidiosis, Microsporidiosis, Entamoeba histolytic Table 5-3: Mycobacterial Infections M. tuberculosis, M. avium, M. kansasii, M. haemophilum, M. gordonae, M. genavense, M. xenopimalonoense, M. chelonei Table 5-4: Viruses Herpes simplex, Herpes zoster, Cytomegalovirus retinitis, Progressive multifocal leukoencephalopathy Table 5-5: Bacteria Streptococcus pneumoniae, Bartonella henselea/ quintana, Haemophilus influenzae, Nocardia asteroidePseudomonas aeruginosa, Rhodococcus equi, Salmonella, Staphylococcus aureus, Treponema pallidum Table 5-6: Treatment of Miscellaneous and Non-Infectious Disease Complications/Classified by Organ Syste Table 5-6A: Cardiac Table 5-6H: Gastrointestinal Table 5-6B: Pulmonary Table 5-6I: Hepatobiliary Table 5-6C: Renal Table 5-6J: Wasting Table 5-6D: Neurologic Table 5-6K: Pain Table 5-6E: Hematologic Table 5-6L: Psychiatric and Sleep Disorders Table 5-6F: Tumors Table 5-6M: Terminal Illness Table 5-6G: DermatologicTable 5-6: Continued - Treatment of Miscellaneous and Non-Infectious DiseaseComplications/Classified by Organ SystemCondition Treatment Comment5-6L: Psychiatric & Sleep Disorders Anxiety Nonbenzodiazepine-nonbarbiturate; dependence liab negligible; increase dose 5 mg every 2 to 4 days to effe Buspirone (BuSpar) 5 mg tid dose of 15-30 mg. Nortriptyline: Titrate level (70-125 ng/dL); Major side effects are nausea, nervousness, insomnia, weight loss, d promotes sleep constipation; insomnia may be treated with Desyrel 25-50 mg hs. Desipramine (<125 kg/dL); promotes sleep.
    • Depression Fluoxetine (Prozac) 10 mg increasing to 20 HAART with immune reconstitution is associated with mg qd substantial improvement in despression (J AIDS 2000;1 Nortriptyline (Pamelor) 10-25 mg hs Major side effects are nausea, nervousness, insomnia, weight loss, d constipation; insomnia may be treated with Desyrel 25-50 mg hs. increasing to 50-150 mg hs or desipramine (Norpramin) 10-25 mg hs increasing to 50-200 mg hs Nortriptyline: Titrate level (70-125 ng/dL); promotes sl Desipramine (<125 ng/dL); promotes sleep. Sertraline (Zoloft) 25-50 mg/day increasing to 50-150 mg/day Side effects are similar to those noted for Prozac; but due to shorter half-life. Paroxetine (Paxil) 20-50 mg PO/day Promotes sleep Bupropion (Wellbutrin) 150 mg qd of SR formulation; increase to 300 mg/day on day 3 p.r.n. Promotes sleep Mirtazapine (Remeron) 15 mg hs; increase to 15-45 mg/day Dose 2-3x/day or dose once daily with extended relea (Effexor XR) Nefazodone (Serzone) 100 mg bid increasing to 300-600 mg/day Venlafaxine HCI (Effexor) 37.5-75 mg/day increasing to 75-150 mg/day Delirium Haldol (0.5-1mg) hs Insomnia Diphenhydramine (Benadryl) 25-50 mg hs Nonprescription. Trazodone (Desyrel) 25-100 mg PO hs Chloral hydrate 500-1000 mg PO hs Class IV, but often considered one of the safest and l habit-forming sedatives. Zolpidem (Ambien) 5-10 mg hs Nortriptyline or amitriptyline 25-50 mg hs Apathy & Utility confirmed for Ritalin and Pemoline for fatigue aFatigue with depression and psychological distress (Arch Intern Ritalin 7.5 mg bid with weekly increases to 2001;161:411). intolerance (hyperactivity) or maximum of 60 mg/day Pemoline 18.75 mg (1 cap) bid with weekly increases to intolerance (shakiness) or maximum of 150 mg (8 caps)/day
    • 1. Detoxification: Sometimes with long actingSubstance benzodiazepinesabuse 2. Treatment of comorbid conditions: mental heatlh (depression, bipolar disorder, schizophrenia, personality disorders, etc.), medical conditions, and chronic pain syndromes. 3. Maintenance treatment and relapse prevention: individualized to patient need5-6M: Terminal Illness Morphine or other opioids orally or Patients given opioids for acute pain or cancer pain ra parenterally; experience euphoria and rarely develop psychologic de clinically significant physical dependence develops afte MS Contin (continuous-release morphine) weeks with large doses. PO 15, 30, 60, or 100 mg; usual dose is 15-60 mg PO q12h Patient-controlled analgesia (PCA) for morphine Methadone (above doses) Fentanyl patch Top of Page | Chapter VI: Drugs - Guide to InformationCopyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rights reserved.* Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained in this site because noreference or service can take the place of medical training, education, and experience. Consumers are cautioned that this site is not intended to provideadvice about any specific medical condition they may have or treatment they may need and they are encouraged to call or see their physician or other hprovider promptly with any health related questions they may have.
    • Go to a Chapter Table of Contents Natural Historyand Classification Laboratory Tests Disease Prevention Antiretroviral TherapyManagement of Opportunistic Infections Drugs: Guide to Information SystemsReview HIV in Corrections VI. Drugs: Guide to InformationUnderstanding Drug ProfilesListings are alphabetical by generic name (except for Trizivir).Trade name and pharmaceutical company source are provided unless there are multiple providers.Cost is based on average wholesale price (AWP) according to Price Alert, First DataBank, San BruFebruary 15, 2001. Prices are generally given for generic products when generics are available.Pharmacology, side effects, and drug interactions: Data are from Drug Information 2000; AmeriFormulary Service, Bethesda, Md.; PDR-2001.Creatinine clearance:Males: Weight (kg) x (140-age in years)/72x serum creatinine (mg/dL)Females: Determination for males x 0.85Note:1) Obese patients - use lean body weight.2) Formula assumes stable renal function. Assume creatinine clearance (CrCl) of 5-8 mL/min for paanuria or oliguria.3) Pregnancy and volume expansion: GFR may be increased in third trimester of pregnancy and witparenteral fluids.Patient Assistance Programs: Most pharmaceutical companies that provide this service require: 1eligibility criteria such as an annual income <$12,000 for an individual or <$15,000 for a family and 2non-availability of prescription drug payment from public or private third party sources. Most requireand a letter of verification, and most will provide a 3 month supply subject to re-review at that time (http://www.needymeds.com).Classification of controlled substance:Category InterpretationI High potential for abuse and no current accepted medical use. Examples are heroiII High potential for abuse. Use may lead to severe physical or psychological dependenc are opiods, amphetamines, short-acting barbiturates, and preparatins containing codeine Prescriptions must be written in ink or typewritten and signed by the practitioner. Verbal must be confirmed in writing within 72 hours and may be given only in a genuine emerge
    • II High potential for abuse. Use may lead to severe physical or psychological dependenc are opiods, amphetamines, short-acting barbiturates, and preparatins containing codeine Prescriptions must be written in ink or typewritten and signed by the practitioner. Verbal must be confirmed in writing within 72 hours and may be given only in a genuine emerge renewals are permitted.III Some potential for abuse. Use may lead to low-to-moderate physical dependence or h psychological dependence. Examples are barbiturates and preparations containing sma codeine. Prescriptions may be oral or written. Up to five renewals are permitted within siIV Low potential for abuse. Examples include chloral hydrate, phenobarbital, and benzod Use may lead to limited physical or psychological dependence. Prescriptions may be ora Up to five renewals are permitted within six months.V Subject to state and local regulation. Abuse potential is low; a prescription may not b Examples are antitussive and antidiarrheal medications containing limited quantities of oClassification for use in pregnancy based on FDA categories: Ratings range from "A" for drugsbeen tested for teratogenicity under controlled conditions without showing evidence of damage to thand "X" for drugs that are definitely teratogenic. The "D" rating is generally reserved for drugs with nalternatives. The "X" rating means there is absolutely no reason to risk using the drug in pregnancy.Category InterpretationA Controlled studies show no risk. Adequate, well-controlled studies in pregnant wome to demonstrate risk to the fetus.B No evidence of risk in humans. Either animal findings show risk, but human findings d no adequate human studies have been done, animal findings are negative.C Risk cannot be ruled out. Human studies are lacking, and animal studies are either po risk, or lacking as well. However, potential benefits may justify the potential risk.D Positive evidence of risk. Investigational or postmarketing data show risk to the fetus. Nevertheless, potential benefits may outweigh the potential risk.X Contraindicated in pregnancy. Studies in animals or humans, or investigational or pos reports, have shown fetal risk which clearly outweighs any possible benefit to the patienPregnancy registry for antiretroviral drugs: This is a joint project sponsored by staff from pharmacompanies with an advisory panel with representatives from the CDC, NIH obstetrical practitioners,pediatricians. The registry allows anonymity of patients and birth outcome follow-up is obtained by reHealthcare professionals should report prenatal exposures to antiretroviral agents to: Antiretroviral PRegistry, 155 N. Third Street, Suite 306, Wilmington, NC 28401; 800-258-4263; fax 800-800-1052. Table of Contents | Top of Page | Next page -- AbacavirCopyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rights reserved.* Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained in this site because no sservice can take the place of medical training, education, and experience. Consumers are cautioned that this site is not intended to provide medical advmedical condition they may have or treatment they may need and they are encouraged to call or see their physician or other health care provider promprelated questions they may have.
    • Go to a Chapter Table of Contents Natural Historyand Classification Laboratory Tests Disease Prevention Antiretroviral TherapyManagement of Opportunistic Infections Drugs: Guide to Information SystemsReview HIV in Corrections VI. Drugs Guide to InformationAbacavir (ABC)Trade name: Ziagen (GlaxoSmithKline)Forms and price: 300 mg tabs @$6.41/tab or $4769/year, oral suspension with 20 mg/mL; availabTrizivir tabs with AZT (300 mg), 3TC (150 mg), and ABC (300 mg) for bid administration at $16/tabUsual regimen: ABC 300 mg tabs PO bid (no food restrictions) Trizivir - 1 tab bid (no food restrictions)Class: Nucleoside analogTrials: With monotherapy, ABC reduced viral load 1.5-2.0 logs-significantly more than other nucleoThe first major comparative trial was CNA 3003 (ABC/AZT/3TC vs AZT/3TC) in 173 treatment-naïvpatients with CD4 cell count >100/mm3. At 24 weeks, 70% of those in the three drug arm had viral lc/mL, and the average increase in CD4 cell count was 86/mm3. This was significantly better than rethe AZT/3TC arm. The response at 48 weeks was sustained; however, a subset analysis of participbaseline viral loads of >100,000/mL demonstrated that only 33% achieved undedectable virus (6thChicago, Ill., February 1999, Abstract 16).CNA 3005 compared the triple NRTI regimen (ABC/AZT/3TC) with IDV/AZT/3TC in 562 treatment-patients. At 48 weeks 51% in both groups had achieved viral load <400 c/mL by intent-to-treat anal31% receiving the ABC regimen with a baseline viral load >100,000 c/mL had reduction to <400 c/mcompared with 45% in the IDV arm (Antiviral Therapy 1999;4(S1):52). There was comparable immurestoration in the two groups with median CD4 cell count increases of about 140/mm3. Genotypic reanalysis of HIV strains from 43 virologic failures on AZT/3TC/ABC at 96 weeks showed that the maresistance mutation was M184V in 35% (8th CROI, Chicago, Ill., February 2001, Abstract 448).In nucleoside-experienced patients, the efficacy of ABC has been disappointing. In the expanded aprogram that included 2200 patients who failed standard therapy with two nucleosides plus a PI anCD4 cell counts <100/mm3 and viral loads >30,000 c/mL, only 25% experienced a reduction in viral>0.5 log with the addition of ABC. In study 3002, patients receiving any prior regimen with viral load500-50,000 c/mL had their regimens "intensified" with ABC. At 8 weeks, 39% of ABC recipients hadload <400 c/mL. There was no difference between those with or without prior 3TC experience or thmutation.
    • CD4 cell counts <100/mm and viral loads >30,000 c/mL, only 25% experienced a reduction in viral>0.5 log with the addition of ABC. In study 3002, patients receiving any prior regimen with viral load500-50,000 c/mL had their regimens "intensified" with ABC. At 8 weeks, 39% of ABC recipients hadload <400 c/mL. There was no difference between those with or without prior 3TC experience or thmutation.CNA 2006 was a nonrandomized study of ABC/APV in treatment-naïve patients with CD4 cell coun>400/mm3. By intent-to-treat analysis at 72 weeks, 68% had viral load <50 c/mL and 40% had viralc/mL. The mean CD4 cell count increase was 239/mm 3 (7th CROI, San Francisco, Calif., FebruaryAbstract 336).CNA 2007 involved the use of ABC/APV/EFV as a salvage regimen for patients with viral load >50receiving PI-containing regimens for >20 weeks. At 16 weeks, 26% achieved viral load <400 byintent-to-treat analysis. The best results were seen in patients with low viral load at entry and in patnaïve to NNRTIs.The Swiss Cohort Study examined patients who responded to PI-containing regimens and were therandomized to continue the PI regimen or switch to a triple NRTI regimen with ABC/AZT/3TC. At 48viral load and CD4 cell count responses were comparable in both groups, and blood lipid profiles win the triple NRTI group (7th CROI, San Francisco, Calif., February 2000, Abstract 457).In summary, ABC is a potent NRTI, although experience with combination treatment using antiretrodrugs other than AZT/3TC is limited. The "triple nuke" regimen is an appropriate option for initial theselected patients with the advantages of preserved options, probable reduction in lipodystrophy, anconvenient dosing regimen. Disadvantages include the hypersensitivity reactions and possible redupotency in patients with high baseline viral loads. ABC does not appear to be effective as a componsalvage therapy in patients with extensive NRTI experience. Some authorities advocate the additioto the regimens containing AZT + 3TC, since this increases potency with minimal risk of increasedresistance. Others would advocate reserving ABC for intensification. The combination of ABC + 3Tdual NRTI component of HAART is attractive due to good tolerance, low potential for mitochondrialand no thymidine analogue mutations after failure; disadvantage is paucity of experience.In vitro activity: The IC 50 vs HIV-1 is 0.07-1.0 µM. There is synergy when ABC is combined with Aand AZT; activity is additive when ABC is combined with ddI, 3TC, d4T, and ddC.Resistance: ABC selects for the follwoing mutations on the RT gene: 65, 74, 115, and 184. The 18mutation lead to complete cross-resistance to 3TC, but by itself does not significantly decrease ABCsusceptability. Mutations at codons 65, 74, and possibly 184 lead to cross resistance to ddI and ddCof these mutations results in a 2- to 4-fold decrease in susceptability to ABC. Significant resistancemultiple mutations, usually in addition to the 184 mutation. Clinical trials indicate that the presence oM184V mutations plus at least 3 thmidine and log mutations (TAMs) predicts ABC failure.Indications: see Chapter 4Pharmacology Bioavailability: 83%; alcohol increases ABC levels by 41%. T½: 1.5 hours (serum); intracellular T½ -3.3 hours. CSF levels: 27% to 33% serum levels Elimination: 81% metabolized by alcohol dehydrogenase and glucuronyl transferase with ren excretion of metabolites; 16% recovered in stool and 1% unchanged in urine. (Metabolism do not involve the cytochrome P450 pathway.) Dose modification in renal failure: NoneSide effects: Hypersensitivity reaction: This serious and potentially lethal side effect is noted inpatients. Clinical features include fever (usually 39 o to 40oC), skin rash (maculopapular or urticarial)malaise, GI symptoms (nausea, vomiting, diarrhea, abdominal pain), arthralgias, cough and/or dyspSome patients do not develop the rash. Laboratory changes may include increased CPK, elevated
    • Dose modification in renal failure: NoneSide effects: Hypersensitivity reaction: This serious and potentially lethal side effect is noted inpatients. Clinical features include fever (usually 39 o to 40oC), skin rash (maculopapular or urticarial)malaise, GI symptoms (nausea, vomiting, diarrhea, abdominal pain), arthralgias, cough and/or dyspSome patients do not develop the rash. Laboratory changes may include increased CPK, elevatedfunction tests, and lymphopenia. These clinical and laboratory findings usually occur within the firstof therapy and the median time of onset is 9 days (Lancet 2000;356:1423). There are no clearly defactors (8th CROI, Chicago, Ill., February 2001, Abstract 621). Rechallenge has been associated wdefinite drug-associated mortality in at least three patients. A comparison of symptoms of ABChypersensitivity in 15 patients and influenza in 30 patients showed that flu is less likely to cause GIsymptoms, but there was considerable overlap (8th CROI, Chicago, Ill., February 2001, Abstract 62Hypersensitivity reactions should be reported to the Abacavir Hypersensitivity Registry at 800-270-0Patients should be warned to consult their provider immediately if they note skin rash/fever, typicalsymptoms, cough, dyspnea, or constitutional symptoms, especially during the first month of therapywarning sheet is available from pharmacists. Other side effects include nausea, vomiting, malaise,headache, diarrhea, or anorexia. Patients may develop lactic acidoses with or without hepatic steatABC appears to be an infrequent cause of mitochondrial toxicity compared to other NRTIs.Drug interactions: Alcohol increases ABC levels by 41%; no effect on alcohol levels (Antimicrob AChemother 2000;283:1811).Pregnancy: Class C. Rodent teratogen test showed skeletal malformations and anasarca at 35x thcomparable human dose. Placental passage positive in rats. Top of Page | Table of Contents | Next page -- AcyclovirCopyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rights reserved.* Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained in this site because noreference or service can take the place of medical training, education, and experience. Consumers are cautioned that this site is not intended to provideadvice about any specific medical condition they may have or treatment they may need and they are encouraged to call or see their physician or other hprovider promptly with any health related questions they may have.
    • Go to a Chapter Table of Contents Natural Historyand Classification Laboratory Tests Disease Prevention Antiretroviral TherapyManagement of Opportunistic Infections Drugs: Guide to Information SystemsReview HIV in Corrections VI. Drugs Guide to InformationAcyclovirTrade name: Zovirax (GlaxoSmithKline) or genericForms and price: 200 mg caps - $1.05/cap 400 mg tabs - $2.13/tab 800 mg tabs - $4.01/tab 200 mg/5 cc suspension - $93.55/473 mL or $0.82/200 mg 500 mg and 1 g vials (IV) - $10.00/500 mg (generic) 5% ointment, 3 g - $21.31; 15 g - $49.22 (utility limited)Class: Synthetic nucleoside analog derived from guaninePatient assistance program: 800-722-9294.Indications and dose (Regimens suggested are based on PDR 2001; MMWR 1993;42[RR-14]:1;Pract 1992;2:100; JAMA 1991;264:747; N Engl J Med 1983;308:916; N Engl J Med 1986;314:144;Med 1989;320:293; N Engl J Med 1991;325:551; Ann Intern Med 1992;117:358; MMWR 1998;47[R HSV* First episode genital 400 mg PO q8h x 11 to 14 days, 5 mg/kg IV q8h x 5 to 7 days up to 800 mg 5x/day PO, or 15 mg/kg/day IV for severe or refractory cases. Recurrent: 400 mg PO tid or 800 mg PO bid x 5 days; AIDS patients may require higher doses. Perirectal: 400 mg PO 5x/day x 10 days Progressive mucocutaneous: 5-10 mg/kg IV q8h x 7 to 14 days Prophylaxis: 400 mg PO bid (this is standard dose in immunocompetent patients); 400 mg PO 3 to 5x/day may be required for AIDS patients. Prophylaxis is contraindicated in pregnancy. Acyclovir-resistant: Doses up to 800 mg 5x/day PO or 10 mg/kg IV q8h or by constant infusion (or foscarnet, 40 mg/kg IV q8h) Note: There is a good correlation between in vitro activity and in vivo response. Probability of failure with acyclovir-resistant strains using standard doses of acyclovir is 95% (Antimicrob Agents Chemother 1994;38:1246). Valacyclovir or famciclovir are frequently preferred agents for oral treatment of HSV or VZV.
    • Acyclovir-resistant: Doses up to 800 mg 5x/day PO or 10 mg/kg IV q8h or by constant infusion (or foscarnet, 40 mg/kg IV q8h) Note: There is a good correlation between in vitro activity and in vivo response. Probability of failure with acyclovir-resistant strains using standard doses of acyclovir is 95% (Antimicrob Agents Chemother 1994;38:1246). Valacyclovir or famciclovir are frequently preferred agents for oral treatment of HSV or VZV. VZV* Primary (Chickenpox): 800 mg PO 5x/day x 7 to 10 days Dermatomal zoster (shingles): 10 mg/kg IV q8h x 7 days or 800 mg PO 5x/day x 7 days (Famciclovir or valacyclovir are preferred for oral therapy of shingles) due to easier adherence, better efficacy, or improved drug levels. Disseminated zoster: 10 mg/kg IV q8h x 7 days Acyclovir-resistant: Foscarnet (40 mg/kg IV q8h) Note: Varicella vaccine is a live-virus vaccine and is contraindicated in HIV-infected people. EBV, Oral hairy leukoplakia: 800 mg PO 5x/day x 2 to 3 weeks, then 1.2 - 2.0 g/day. (Most cases are not treated, and those that are usually relapse after treatment. Ganciclovir is also effective.) *Acyclovir or other antiviral agent should be started within 24 hours of the exanthem with HSV and within 4 day while new lesions are still forming with dermatomal zoster or chicken pox.Pharmacology Bioavailability: 15% to 20% with oral administration T½: 2.5 to 3.3 hours, CSF levels: 50% serum levels Elimination: RenalTable 6-1: Acyclovir - Dose Modification in RenalFailureUsual Dose Creatinine Adjusted Dose Clearance200 mg 5x/day >10 mL/min 200 mg 5x/day <10 mL/min 200 mg q12h800 mg 5x/day >50 mL/min 800 mg 5x/day 10-50 mL/min 800 mg q8h <10 mL/min 800 mg q12h5-10 mg/kg IV q8h >50 mL/min 5-10 mg/kg IV q8h 10-50 mL/min 5-10 mg/kg q12h-q24h <10 mL/min 5-10 mg/kg q24hSide effects (infrequent and rarely severe): irritation at infusion site, rash, nausea and vomiting, diarenal toxicity (especially with rapid IV infusion, prior renal disease, and concurrent nephrotoxic drugdizziness, abnormal liver function tests, itching, and headache. Rare complications include: CNS toencephalopathy, disorientation, seizures, hallucinations, anemia, neutropenia, thrombocytopenia, ahypotension.Drug interactions: Increased meperidine and theophylline levels; probenecid prolongs half-life of aPregnancy: Category C: Not teratogenic, but potential to cause chromosomal damage at high doseRegistry shows no increased incidence of fetal abnormalities among 601 women for whom pregnanoutcome data were available (MMWR 1993;42:806). The Registry contact number is 800-258-4263recommends use of acyclovir during pregnancy only for life-threatening disease.
    • Pregnancy: Category C: Not teratogenic, but potential to cause chromosomal damage at high doseRegistry shows no increased incidence of fetal abnormalities among 601 women for whom pregnanoutcome data were available (MMWR 1993;42:806). The Registry contact number is 800-258-4263recommends use of acyclovir during pregnancy only for life-threatening disease.Table 6-2: Activity of Antivirals AgainstHerpesviruses HSV VZV EBV CMV HHV 6-8Acyclovir ++ + + -- --Famciclovir ++ + + -- --Valacyclovir ++ + + -- --Ganciclovir ++ + ++ ++ +Foscarnet + + ++ + +Cidofovir + + ++ + ++Table 6-3: Comparison of Drugs for Infections Caused by Herpes Simplex and Varicella ZosN Engl J Med 1999;340:1255) Duration Acyclovir Valacyclovir FamciclovirHerpes simplexGenitalFirst episode 7 to 10 days 400 mg tid 1 g bid 250 mg tidRecurrent 5 days 400 mg tid 500 mg bid 125 mg bidSuppression Years 400 mg tid 500 mg qd or 125-250 mg bid 500 mg bidSevere disease >5 days 5-10 mg/kg/day q8h IV 1 g tid --Perirectal 7 to 10 days 800 mg tid -- --Oral HSV Treatment 5 days 200 mg 5x/day -- -- Prophylaxis -- 400 mg bid -- --Mucocutaneous progressive 7 to 14 days 400 mg 5x/day 1 g tid -- 5 mg/kg q8h IVAcyclovir-resistant -- -- -- --Varicella zosterDermatomal 7 days 800 mg 5x/day 1 g tid 500 mg tid 10 mg/kg q8h IVDisseminated 7 days 10 mg/kg q8h IV -- --Acyclovir-resistant -- -- -- --*HSV resistant or refractory to treatment with acyclovir may be treated with topical or intravenous cidofovir (J Infect Dis 1997;176:892; Antimicrob Age 1995;39:2120; Clin Infect Dis 1994;18:570), topical trifluridine (J AIDS 1996;12:147) or foscarnet (N Engl J Med 1991;325:551). Top of Page | Table of Contents | Next page -- Agenerase
    • Copyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rightsreserved.* Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained inthis site because no single reference or service can take the place of medical training, education, and experience. Consumers arecautioned that this site is not intended to provide medical advice about any specific medical condition they may have or treatmentthey may need and they are encouraged to call or see their physician or other health care provider promptly with any health relatedquestions they may have.
    • Go to a Chapter Table of Contents Natural Historyand Classification Laboratory Tests Disease Prevention Antiretroviral TherapyManagement of Opportunistic Infections Drugs: Guide to Information SystemsReview HIV in Corrections VI. Drugs Guide to InformationAgeneraseSee Amprenavir Top of Page | Table of Contents | Next page -- AlbendazoleCopyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rightsreserved.* Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained inthis site because no single reference or service can take the place of medical training, education, and experience. Consumers arecautioned that this site is not intended to provide medical advice about any specific medical condition they may have or treatmentthey may need and they are encouraged to call or see their physician or other health care provider promptly with any health relatedquestions they may have.
    • Go to a Chapter Table of Contents Natural Historyand Classification Laboratory Tests Disease Prevention Antiretroviral TherapyManagement of Opportunistic Infections Drugs: Guide to Information SystemsReview HIV in Corrections VI. Drugs: Guide to InformationAlbendazoleTrade name: Albenza (GlaxoSmithKline)Form: 200 mg tablets; $1.32/200 mg tab available from SmithKline 800-877-7074Dose: 400-800 mg PO bid x >3 weeks, usually 400 mg/day PO x 3 weeksIndication: MicrosporidiosisClinical Trials: Albendazole (400 mg bid x 3 weeks) is highly effective with microsporidiosis involviEncephalitozoon (septata) intestinalis, but is less effective or not effective for Enterocytozoon bienePharmacology Bioavailability: Low, but absorption is increased 5-fold if taken with a fatty meal vs administration in a fasting state. Should be taken with fatty meal. T½: 8 hours Elimination: Metabolized in liver to albendazole sulfoxide, then excreted by enterohepatic circulation. Dose modification in renal failure: NoneSide effects: Hepatotoxicity and reversible pancytopenia or neutropenia – monitor CBC and liver futests at least every 2 weeks.Pregnancy: Category C. Albendazole is teratogenic and embryotoxic in rodents. Top of Page | Table of Contents | Next page -- AlprazolamCopyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rights reserved.* Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained in this site because no
    • Copyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rights reserved.* Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained in this site because noreference or service can take the place of medical training, education, and experience. Consumers are cautioned that this site is not intended to provideadvice about any specific medical condition they may have or treatment they may need and they are encouraged to call or see their physician or other hprovider promptly with any health related questions they may have.
    • Go to a Chapter Table of Contents Natural Historyand Classification Laboratory Tests Disease Prevention Antiretroviral TherapyManagement of Opportunistic Infections Drugs: Guide to Information SystemsReview HIV in Corrections VI. Drugs: Guide to InformationAlprazolamTrade name: Xanax (Upjohn)Forms and price (generic form): 0.25 mg tab - $0.46; 0.5 mg tab - $0.70; 1 mg tab - $0.77; 2 mg$1.64Class: Benzodiazepine, controlled substance category IVIndications and dose regimen: Anxiety: 0.25-0.5 mg tid; increase if necessary at intervals of 3 to 4 days to maximum of 4 mg/day. Panic disorder: 0.5 mg tid with increase at increments of <1 mg/day to maximum of 6-10 mg/day Dose reduction or withdrawal: Decrease by <0.5 mg q 3 days; some suggest decrease by mg at 3 to 7 intervalsPharmacology Bioavailability: >90% T½: 11 hours, prolonged with obesity and hepatic dysfunction Elimination: Metabolized and renally excretedSide Effects: see Benzodiazepines. Seizures, delirium, and withdrawal symptoms with rapid doseor abrupt discontinuation. Withdrawal symptoms at 18 hours to 3 days after abrupt discontinuation.usually occur at 24 to 72 hours after abrupt withdrawal.Drug interactions: Additive CNS depression with other CNS depressants including alcohol. Disulfcimetidine prolong the half-life of alprazolam. Levels of alprazolam are increased by some PIs, butconcurrent use is not contraindicated.Relative contraindications: History of serious mental illness, drug abuse, alcoholism, open-angleglaucoma, seizure disorder, severe liver disease.Pregnancy: Category D; fetal harm - contraindicated; possible role in cleft lip and heart abnormaliti
    • Relative contraindications: History of serious mental illness, drug abuse, alcoholism, open-angleglaucoma, seizure disorder, severe liver disease.Pregnancy: Category D; fetal harm - contraindicated; possible role in cleft lip and heart abnormaliti