Medical management of hiv infection

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Medical management of hiv infection

  1. 1. 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.
  2. 2. 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.
  3. 3. 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.
  4. 4. 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.
  5. 5. 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.
  6. 6. 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
  7. 7. 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
  8. 8. 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.
  9. 9. 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
  10. 10. 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
  11. 11. 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.
  12. 12. 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.
  13. 13. 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.
  14. 14. 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
  15. 15. 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.
  16. 16. 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
  17. 17. 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.
  18. 18. 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.
  19. 19. 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.
  20. 20. 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.
  21. 21. 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.
  22. 22. 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%)
  23. 23. 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.
  24. 24. 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
  25. 25. 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
  26. 26. 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%
  27. 27. 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).
  28. 28. 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.
  29. 29. 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
  30. 30. 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).
  31. 31. 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.
  32. 32. 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
  33. 33. 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
  34. 34. 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
  35. 35. 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.
  36. 36. 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

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