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  1. 1. HISTORICAL BACKGROUND HIV- Global Pandemic 1981-1st case in USA 1983-HIV isolated 1984-HIV Confirmed as Causative agent 1985-ELISA developed
  2. 2. INDIAN SCENARIO First case – 1986. India now 3rd in World. Low rate of Infection Prevalence rate is 0.#%.More prevalent in Southern/North-Eastern states. Highest adult prevalence is 1.4% (Manipur) U/R prevalence is 0.35/0.25 %. PLHA -1.4-1.6 million. UN 2011 AIDS – 50% decline in 10 yrs.
  3. 3. HIV
  4. 4. HIV Retrovirus Types:- HIV1,HIV2 RNA Virus Icosahedral Has numerous spikes . Envelope has gp120 & gp41. Reverse transcriptase –hallmark. Affects CD4 T-lymphocytes. CD4 – 55 kDA protein CCR-5,CXCR4 – Co-receptors
  5. 5. PRE-ART Care HIV+ve not requiring ART Counseling to maintain healthy and positive living. Comprehensive medical history and exam. Baseline lab-Test. Follow-up visits – Pre ART care and CD4 screening Reporting to ARTC if unwell. Family screening and counseling. Registration.
  6. 6. Monitoring and Follow-up CD4 Count Repeat at<350 and not on ART 3 months>350 and not on ART 6 monthsOn ART (any value) 6months>500 Annual Screening
  7. 7. WHO Clinical staging of HIV/AIDS for adults and adolescents, 2006 Clinical stage 1 Asymptomatic Persistent generalized lymphadenopathy
  8. 8. Clinical stage 2 Unexplained moderate weight loss (< 10% of presumed or measured body weight) Recurrent respiratory tract infections (sinusitis, tonsillitis, otitis media, pharyngitis) Herpes zoster Angular cheilitis Recurrent oral ulceration
  9. 9.  Papular pruritic eruptions Seborrhoeic dermatitis Fungal nail infections Clinical stage 3 Unexplained severe weight loss (>10% of presumed or measured body weight) Unexplained chronic diarrhea for longer than one month
  10. 10.  hairy leukoplakia Persistent oral candidiasis Unexplained persistent fever Severe bacterial infections. Acute necrotizing ulcerative stomatitis, gingivitis or periodontitis Unexplained anaemia (<8g/dl), neutropenia(<5x10/litre) and or chronic thrombocytopenia (<50 X 10/litre
  11. 11. Clinical Stage 4 HIV Wasting Syndrome Pneumocystis Syndrome Recurrent severe bacterial pneumonia Chronic herpes simplex infection (Orolabial,genital or anorectal of more than one monts duration or visceral at any site) Oesophageal candidiasis (or candidiasis of trachea,bronchi or lungs)
  12. 12.  Extrapulmonary tuberculosis Kaposi Sarcoma Cytomegalovirus infection (retinitis or infection of other organs) Central Nervous system toxoplasmosis HIV encephalopathy Extra Pulmonary Cryptococcosis including meningitis. Disseminated non-tuberculous mycobacteria infection
  13. 13.  Progressive multifocal leukoencephalopathy Chronic Cryptosporidiosis Chronic Isosporiasis Disseminated mycosis (Extrapulmonary histoplasmosis,Coccidomycosis) Recurrent Septicaemia (including non- typhoidal salmonella)
  14. 14.  Lymphoma (Cerebral or B Cell non- Hodgkin Invasive Cervical; Carcinoma Atypical disseminated leishmaniasis Symptomatic HIV-associated nephropathy or symptomatic HIV- associated cardiomyopathy
  15. 15. CO-TRIMOXAZOLE PROPHYLAXIS (CPT) Indications – WHO Clinical stage 3&4 - CD4 <200 Cell/cumm. - CD4<350 Cell/Cumm(Symp.) - PCP treated with CD4>200 Cells/cumm - Dose double strength TMP-SMX - Alternative Drug-Dapsone - Dose 100mg OD
  16. 16. Protocol for Co-trimoxazole desensitization Protocol for Co-trimoxazole desensitization Step Dosage Dosage 80 mg SMX + 16 mg TMP (2ml oral suspension)Day1 mg SMX + 32 80 mg SMX + 16 mg TMPsuspension) 160 mg TMP (4ml oral (2ml oral suspension)Day2 mg SMX + 48 mg TMP SMX + 32(6ml oral suspension) 240 160 mg mg TMP (4ml oral suspension) 320 mg SMX + 64 mg TMP (8 ml oral suspension)Day3 240 mg SMX + 48 mg TMP (6ml oral suspension) One single-strength SMX-TMP tablet (400 mg SMX + 80 mg TMP)Day4 320 mg SMX + 64 mg TMP (8 ml oral suspension) Two single-strength SMX-TMP tablets (800 mg SMZ + 160 mg TMP)Day5 double-strength tablet or one One single-strength SMX-TMP tablet (400 mg SMX + 80 mg TMP)Day6 Two single-strength SMX-TMP tablets (800 mg SMZ + 160 mg TMP) or one double-strength tablet
  17. 17. HAART Mainstay of treatment Combination of 3 or more drugs. Interrupt Viral replication. Not a cure but prolongs life. Has changed HIV into a chronic disease. To be taken lifelong Aim – low viral load Reduces drug resistance Important role in PMTCT.
  18. 18. Classes of ARV DrugsNucleoside reverse Non-Nucleoside Protease inhibitorstranscriptase reverse (PI)inhibitors (NRTI) transcriptase inhibitors (NNRTI)Zidovudine Nevarapine (NVP) Saquinavir (SQV)(AZT/ZDV)Stavudine (d4T) Efavirenz (EFV) Ritonavir (RTV)Lamivudine (3TC) Delavirdine (DLV) Nelfinavir (NFV)Didanosine (ddl) Amprenavir (APV)
  19. 19. Zalcitabine (ddC) Fusion Inhibitors Indinavir (INV) (FI)Abacavir (ABC) Enfuvirtide (T-20) Lopinavir/Ritona vir (LPV)Emtricitabine Integrase Foseamprenavir Inhibitors (New) (FPV)(NtRTI) CCR5 Entry Atazanavir (ATV) Inhibitor (new)Tenofavir (TDF) Maturation Tipranavir (TPV) Inhibitors(new)
  20. 20. Goals of ART Clinical Goals : Prolongation of life and improvement in quality of life Virological Goals : Greatest possible reduction in viral load . Immunological Goals : Immune reconstitution that is both quantitative and qualitative Therapeutic Goals : Rational sequencing of drugs in a fashion that achieves clinical,virological and immunological goals while maintaining treatment options,limiting drug toxicity and facilitating adherence Reduction of HIV transmission in Individuals : Reduction of HIV transmission by suppression of Viral load
  21. 21. Initiation of ART based on CD4 Count and WHO clinical stagingClassification of HIV- WHO Clinical stage CD4 Test not CD4 test available associated clinical available (or result disease pending) Asymptomatic 1 Do not TreatMild Symptoms 2 Do not Treat Treat if CD4<350/cumm Advanced 3 Treat SymptomsSevere/Advanced 4 Treat Treat Symptoms irrespective of CD4 Count
  22. 22. Managing OIs before starting ART Clinical Picture Action Any undiagnosed active Diagnose and treat first;start infection with fever ART when stable TB Treat TB first;start ART as recommended in TB section PCP Treat PCP first;start ART when PCP treatment is completed
  23. 23. ART RegimensZidovudine (AZT) -300mg + Lamivudine (3TC)-150mgStavudine(d4T)-30mg+Lamivudine (3TC)-150mgZidovudine (AZT)-300mg+Lamivudine (3TC) –150mg+Nevi-200mgStavudine(d4T)-30mg + Lamivudine (3TC)-150mg +
  24. 24. Principles of selecting the first-line regimenChoose 3TC (lamivudine) in all regimensChoose one NRTI to combine with 3TC (AZT or d4T)Choose one NNRTI (NVP or EFV)
  25. 25. Monitoring of Patients on ART Basic clinical assessment -Hepatitis -TB/STD -Pregnancy -IDU -Psychiatric diseases -Traditional medications -Weight -Readiness/Commitment of patients.
  26. 26. Mandatory Lab. Tests  -Haemogram  -Blood Sugar  -LFT/RFT/Urine exm.  -Lipid Profile  -VDRL  -CXR  CD4 Count  Viral Load
  27. 27. ART in pregnancy Risk of HIV 14-48% More than 2/3 transmission during labour ART decreases vertical transmission. Dual Goal-maternal HIV/PMPCT
  28. 28. When to start ART in Pregnant women1 Do not treat Treat if CD4<350cells/cumm2 Do not treat3 Treat4 Treat Treat irrespective of CD4
  29. 29. HIV & TB >60%PLHA develop TB. Commonest OI. Commonest cause of mortality. More drug interactions. More toxicity.
  30. 30. Initiation of first-line ART in relation to anti-TB therapyCD4 cell count Timing of ART in ART(cells/) relation to initiation of Recommendations TB treatment Start ATT first Recommended Start ATT as soon as TB ARTAny Count treatment is tolerated EFV-containing (between 2 weeks and regimens 2 months)
  31. 31. HIV-HBV Co- Infection Hep.B is endemic in india Kills more patients than HIV HIV modifies natural history of HBV Higher progression to advance liver disease Impact of HBV on HIV less known Treatment If chronic active hepatitis start ART irrespective of CD4 Count , if no CAH start ART,if CD4 < 350 cells/cumm
  32. 32. ART in HIV-HBV Co-infection 1st Line AZT + 3TC + EFV AZT + 3TC + NVP Alternative d4T + 3TC + (EFV or NVP) TDF + 3TC + (EFV or NVP) Seroconversion at 1yr - 11-22%
  33. 33. HIV & HCV Co-infection Increased progression of liver disease Increased risk of toxicity with ART Effect of HCV on HIV Uncertain Treatment If chronic active hepatitis start ART irrespective of CD4 Count , if no CAH start ART,if CD4 < 350 cells/cumm ART Regimen same as HBV
  34. 34.  Timing of HCV therapy - Before ART - On ART - CD4 Count > 200 cells/cumm Outcome of HCV Therapy  - genotype 1 : 15-28 %  -genotype 2/3 :60-70%  Combination not to be used  RBV & d4T
  35. 35. 1 st Six months of ART Critical period CD4 Recovery Early Toxicity Mortality IRIS
  36. 36. Treatment of IRIS No Std. guidelines Mostly self limiting Continue ART Stop only if life threatening. Drugs-NSAIDS,Steroids,Thalidomide
  37. 37. ARV Drug Toxicity Self limiting to life threatening Difficult to differentiate between disease and drug toxicity. Intercurrent illnesses to be ruled out OI’s should be treated before ART. Management:- Reassurance Substitution Discontinuation
  38. 38. Side Effects and Common causesTime Side-effects Drugs Short term Nausea,Vomiting,Diarrhoea AZT,TDF,PIs Rash NVP,EFV,Abacavir,Pis Hepatotoxicity NPV,EFV,Pis Drwsiness,Diziness,Confusion and EFV Vivid dreams Anaemia ,neutopenia BM AztTMedium Term suppression,Hyperpigmentation Lactic acidosis d4T, Peripheral neuropathy d4T,ddI Pancreatitis ddILong Term Lipodystrophy ,lypoatrophy D4t,ddI,AZT,PI
  39. 39. Determining ART Failure Work with the patient to resolveDoes the patient issues causing non-adherence.adhere properly to Continue the same first-line regimen,ART? give of prophylaxis if necessary and follow closely.Reassess and determine need for second-line therapy.Start second-line regimen only after good adherence can be ensure Signs or symptoms of IRIS Patient has or oi manage IRIS oi, Been on ART for especially TB. Last 6 months
  40. 40. Diagnose treatment failure C if oi present and on ART>6months with good adherence,if CD4 not available Rule out the other causes Cd4 indicating such as IRIS and continuefailure of treatment first-line ART.Patient on ART- last 6 monthsPrepare thepatient for second-line regimen.Theregimen is likely to be more complex.Make sure the patient understands the new drugs,how to takethem and possible side-effects.Reinforce adherence
  41. 41. Treatment failure Parameters for First-lineregimen(WHO 2006 Guidelines)Clinical New or recurrent WHO stage4failure condition after at least 6 months of ART.Immunologic Fall of CD4 Count to pre-therapyal failure baseline or below 50% fall from the on-treatment peakvalue if known Persistent CD4 levels below 100cells/cummVirological Plasma viral load>10,000 copies/mlfailure
  42. 42. Decide What to Give for second-line regimen Second-line regimens should be prescribed by experienced HIV physicians or in consultation with them.The flow chart provides guidanceStep 1 Define treatment failure,see ifDefine treatment failure adherence to treatment is adequate,counsel and support
  43. 43. If AZT is used in first-line,NRTIStep 2 Decide on choices in second-line could be TDF , ABC or ddL.If d4T is used in first-line,NRTI NRTI component choices could be TDF oR ABC.If neither TDF of the second-line nor ABC is available,the last option is ddL+3TC+-AZT).The combination ofregimen. TDF+ddL+ NNRTI is not recommended due to early virological failure and safety concerns. Give only boosted PI inStep 3 combination.The Choices areDecide on the PI LPV/r,ATV/r,IND/r.NLF can beComponent of the used where no cold chain issecond-line regimen. available.It is less potent than a boosted PI.Step4 Include counseling forPatient Education and adherence,linkages to careagreement on treatment plan and support organizations, including followup and outreach services and monitoring follow-up monitoring plan.
  44. 44. List of regimens and Alternatives First-line regimen Second-line regimen NRTI PI Component Component AZT + 3TC + NVP Choices : 1 st LPV/r (heat-stable) AZT + 3TC + EFV Choices: 2 nd ATV/r 1 st TDF + 3 rd SQV/rStandard D4T + 3TC + NVP ABC or 4 th IND/rregimes 2 nd ddL + 5 th NLF ABC or3rd Where no D4T + 3TC + NVP TTF + AZT cold chain ( + - 3TC) available TDF +3TC +NVP Choices1st ddL/ABCSpecial TDF + 3TC + EFV 2 nd ddL/AZT
  45. 45. Effect of Nutrition on HIV/AIDS Optimal Benefits from treatment
  46. 46. Management of occupationalExposure and PEP Avoid exposure to prevent HIV/AIDS Exposure 1)Occupational 2)Non-occupational PEP includes Counseling Risk assessment Relevant Lab. Investigation.
  47. 47. First Aid Short term ART Follow-up & Support Principles of Providing PEP Non-Discrimination Confidentiality Informed Consent
  48. 48. Potentially Infectious Body FluidsExposure to body fluids Exposure to body fluids considered ‘not at Risk’considered ‘at Risk’BloodSemen TearsVaginal secretions SweatCerebrospinal fluidSynovial,pleural,perit Urine and faeces Unless theseoneal, pericardial secretions containfluid Visible bloodAmniotic fluid SalivaOther body fluidsContaminated with
  49. 49. Summaru of Do’s and Don’tDo Do notRemove gloves,if appropriate Do not PanicWash the exposed site Do not put the pricked finger inthoroughly with water mouthIrrigate with water or saline- Do not squeeze the wound toeyes and mouth bleed itWash the skin with soap and Do not usewater bleach,chlorine,alcohol,betadine,io dine or other antiseptics/detergents on the
  50. 50. Categories of ExposureMild Exposure Mucous Memberane/non-intact skin with small volumesModerate Mucous memberane/non-intact skin withExposure small volumes or Exposure with solid needleSevere Exposure Percutaneous with large volumes eg :  an accident with high calibre needle A deep wound Transmission of a significant amount of fluid An accident with material that has been
  51. 51. HIV POST EXPOSUREPROPHYLAXIS Status of SourceExposure HIV+ and Asymptomatic HIV+ and HIV Status Clinically Unknown AsymptomaticMild Consider 2-drug PEP Start 2-drug PEP Usually no PEP or Consider 2-drug PEPModerate Start 2-drug PEP Start 3-drug PEP Usually no PEP or Consider 2-drug PEP
  52. 52. Dosage of the drugs for PEPMedication 2-drug regimen 3-drug regimenZidovudine (AZT) 300 mg twice a day 300 mg twice a dayStavudine(d4T) 30 mg twice a day 30 mg twice a dayLamivudine (3TC) 150 mg twice a day 150 mg twice a dayProtease Inhibitors 1st Choice Lopinavir/ritonavir (LPV/r) 2nd Choice Nelfnavir (NLF)
  53. 53. Regimens to be prescribed byhealth centres Prefered Alternative2-drug regimen (basic PEP 1st Choice : 2nd Choice:Regimen) Zidovudine (AZT) + Stavudine (d4T) + Lamivudine (3TC) Lamivudine (3TC)3-drug regimen (Expanded PEP regimen)- Consult expert opinionfor starting 3rd drug eg LPV/r,NLF or INDNot Recommended ddL+d4T Combination NNRTI such as Nevirapine should not be used in PEP
  54. 54. Follow-up lab. Tests Timing In person taking In persons not taking PEP(Standard regimen) PEPWeeks 2& 4 Transaminases Clinical monitoring Complete blood Counts for hepatitis Week6 HIV-Ab HIV-Ab Month 3 HIV-Ab,anti HCV,HBsAG HIV-Ab,anti HCV,HBsAG Month6 HIV-Ab,anti HIV-Ab,anti -HCV,HBsAG,Transaminas HCV,HBsAG es
  55. 55. Prevention Always better than cure Knowledge of disease Good habits Safe Sex-Barrier methods Loyal to Spouse Sterilized syringes Safe blood/blood products Treatment of STD’s Vaccination
  56. 56. NOAIDS!!!!