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HIV and AIDS

HIV and AIDS. History. 1950s: Blood samples from Africa have HIV antibodies. 1976: First known AIDS patient died. 1980: First human retrovirus isolated (HTLV-1). 1981: First reports of “Acquired Immuno - deficiency Syndrome” in Los Angeles.

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HIV and AIDS

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  1. HIV and AIDS

  2. History • 1950s: Blood samples from Africa have HIV antibodies. • 1976: First known AIDS patient died. • 1980: First human retrovirus isolated (HTLV-1). • 1981: First reports of “Acquired Immuno- deficiency Syndrome” in Los Angeles. • 1983: Virus first isolated in France (LAV). • 1984: Virus isolated in the U.S. (called HTLV-III and AIDS-Related Virus, ARV). • 1985: Development and implementation of antibody test to screen blood donors

  3. History • 1986: Consensus name Human Immunodeficiency Virus (HIV-1), first case in India was detected in Chennai • Related virus (HIV-2) identified • 1992: AIDS becomes the leading cause of death among adults ages 25-44 in the U.S. • 1997: Mortality rates of AIDS starts to decline due to the introduction of new drug cocktails • 2001: World Health Organization predicts up to 40 million infected individuals. More than 22 million have already died.

  4. HIV Virus • RNA virus • HIV-I: A,D: East, West, North, Central Africa B: US, Europe, East Asia, Brazil C: India, South Africa E: Thailand F: East Europe, Brazil HIV-II : West Africa, Brazil, South West Asia Less transmissible Associated with lower viral load , Slower rate of clinical progression Not susceptible to NNRTI, possible PI resistance

  5. HIV Virus Srains • Three groups: "major" group M "outlier" group O "new" group N • Group O - west-central Africa • Group N - discovered in 1998 in Cameroon - is extremely rare • Group M - nine genetically distinct subtypes A, B, C, D, F, G, H, J and K

  6. HIV Viral proteins • gag • pol • env (tat, rev, nef, vif, vpr, vpu) • tev

  7. Life cycle of HIV • Attachment: Virus binds to surface molecule (CD4) of T helper cells and macrophages. - Coreceptors: Required for HIV infection - CXCR4 and CCR5 mutants are resistant to infection • Fusion: Viral envelope fuses with cell membrane, releasing contents into the cell

  8. Life cycle of HIV • Reverse Transcription: Viral RNA is converted into DNA by unique enzyme reverse transcriptase. ‘Reverse transcriptase’ RNA ------------------------> DNA Reverse transcriptase is the target of several HIV drugs: AZT, ddI and ddC. • Integration: Viral DNA is inserted into host cell chromosome by unique enzyme integrase. Integrated viral DNA may remain latent for years and is called a provirus.

  9. Life cycle of HIV • Replication: Viral DNA is transcribed and RNA is translated, making viral proteins. Viral genome is replicated. • Assembly: New viruses are made. • Release: New viruses bud through the cell membrane.

  10. Life cycle of HIV • Replication: Viral DNA is transcribed and RNA is translated, making viral proteins. Viral genome is replicated. • Assembly: New viruses are made • Release: New viruses bud through the cell membrane

  11. High Risk Groups • Promiscuous heterosexual/ homosexual • Commercial sex worker • IV drug abuser • Spouse of HIV infected • Blood recipient

  12. Transmission of HIV (Worldwide) • Sexual contact with infected individual: All forms of sexual intercourse (homosexual and heterosexual); 75% of transmission. • Sharing of unsterilized needles by intravenous drug users and unsafe medical practices; 5-10% of transmission. • Transfusions and Blood Products: Hemophiliac population was decimated in 1980s. Risk is low today; 3-5% of transmission. • Mother to Infant (Perinatal): 25% of children become infected in utero, during delivery, or by breast-feeding (with AZT only 3%); 5-10% of transmission.

  13. Transmission Categories

  14. Pathogenesis Viral transmission 2-3 wks Acute retroviral syndrome 2-3 wks Recovery + Seroconversion 2-4 wks Asymptomatic chronic HIV infection avg 8 yrs Symptomatic HIV infection/AIDS 1-3 yrs Death

  15. Immune abnormalities in HIV • Altered cytokine • Decreased CTL and NK cell function • Decreased humoral and proliferative response to antigens and mitogens • Decreased MHC-II expression • Decreased monocytechemotaxis • Depletion of CD4+ cells • Impaired reactions • Lymphopenia • Polyclonal B-cell activation

  16. Natural History

  17. Stages of HIV Infection

  18. Epidemiology of HIV • Over 40 million people worldwide are HIV positive • 90% of all HIV infections are in the developing countries • 15,000 people are infected with HIV everyday • More than 22 million people, including 3.6 million children, have died from AIDS since the start of the epidemic • India has second highest number of HIV infected people next only to South Africa

  19. Epidemiology of HIV • Major mode of transmission - Heterosexual • HIV-1 is the predominant serotype • HIV-1 subtype C is the commonest • HIV-2 serotype 4% • Dual infection (HIV-1 & HIV-2 : 10%)

  20. A global View of HIV Infection39 Million People(33-46 Million) Living with HIV, 2005

  21. A global View of HIV Infection Total 39.5 (34.1 - 47.1) million Source: Joint United Nations Programme on HIV AIDS (UNAIDS) and WHO 2006

  22. Global summary of the AIDS epidemic December 2006 Source: Joint United Nations Programme on HIV AIDS (UNAIDS) and WHO 2006

  23. Global summary of the AIDS epidemic December 2006 Source: Joint United Nations Programme on HIV AIDS (UNAIDS) and WHO 2006

  24. Revised WHO clinical staging of HIV/AIDS for Adults and Adolescents (2005) • Primary HIV infection • Asymptomatic • Acute retroviral syndrome Clinical stage 1 • Asymptomatic • Persistent generalized lymphadenopathy

  25. Revised WHO clinical staging of HIV/AIDS for Adults and Adolescents (2005) Clinical stage 2 • Moderate and unexplained weight loss (<10% of presumed or measured body weight) • Recurrent respiratory tract infections • Herpes Zoster • Recurrent oral ulcerations • Papular pruritic eruptions • Seborrhoeic dermatitis • Fungal nail infections

  26. Revised WHO clinical staging of HIV/AIDS for Adults and Adolescents (2005) Clinical stage 3 Conditions where a presumptive diagnosis can be made on the basis of clinical signs or simple investigations • Unexplained chronic diarrhoea for longer than one month • Unexplained persistent fever • Severe weight loss (>10% of presumed or measured body weight) • Oral candidiasis • Oral hairy leukoplakia

  27. Revised WHO clinical staging of HIV/AIDS for Adults and Adolescents (2005) Clinical stage 3 • Pulmonary tuberculosis (TB) diagnosed in last two years • Severe bacterial infections • Acute necrotizing ulcerative stomatitis, gingivitis or periodontitis Conditions where confirmatory diagnostic testing is necessary • Unexplained anaemia (< 80 g/l), and or neutropenia (<500/µl) and or thrombocytopenia (<50 000/ µl) for more than one month

  28. Revised WHO clinical staging of HIV/AIDS for Adults and Adolescents (2005) Clinical stage 4 Conditions where a presumptive diagnosis can be made on the basis of clinical signs or simple investigations • HIV wasting syndrome • Pneumocystis pneumonia • Recurrent severe or radiological bacterial pneumonia • Chronic herpes simplex infection (orolabial, genital or anorectal of more than one month’s duration)

  29. Revised WHO clinical staging of HIV/AIDS for Adults and Adolescents (2005) Clinical stage 4 • Oesophagealcandidiasis • Extrapulmonary Tuberculosis • Kaposi’s sarcoma • Central nervous system toxoplasmosis • HIV encephalopathy Conditions where confirmatory diagnostic testing is necessary • Extrapulmonarycryptococcosis including meningitis

  30. Revised WHO clinical staging of HIV/AIDS for Adults and Adolescents (2005) Clinical stage 4 • Disseminated non-tuberculousmycobacteria infection • Progressive multifocal leukoencephalopathy • Candida of trachea, bronchi or lungs • Cryptosporidiosis • Isosporiasis • Visceral herpes simplex infection

  31. Revised WHO clinical staging of HIV/AIDS for Adults and Adolescents (2005) Clinical stage 4 • Cytomegalovirus infection • Any disseminated mycosis (e.g. histoplasmosis, coccidiomycosis, penicilliosis) • Recurrent non-typhoidal salmonella septicaemia • Lymphoma (cerebral or B cell non-Hodgkin) • Invasive cervical carcinoma • Visceral leishmaniasis

  32. WHO revised Clinical staging + Reference range total Lymphocytes : 1500-11400/mm ++ Reference range CD 4 count : 450-1400/mm +++ ARC AIDS- related complex

  33. Clinical Stages (CDC) Primary illness: • Oral candidiasis, lymphadenopathy, Maculopapular rash, Fever, URTI Early symptomatic: • PTB, Recurrent herpes, Herpes zoster, Extragenitalmolluscum, Florid STD Late symptomatic: Septicaemia, Abscess, Wasting, Weight loss, Bacterial pneumonia, Amoebiasis, Drug eruption, Extrapulmonary TB, Seborrheic.dematitis, Psoriasis, Reiters disease

  34. Clinical Stages (CDC) AIDS : Oro-esophageal candidiasis, Cryptococcosis, Toxoplasmosis, PCP, Histoplasmosis, Penicilinosis, CMV, PML, Peripheral neuritis, Encephalopathy, Addisonian pigmentation, Drug rash, Extra pulmonary TB, Weight loss

  35. Aim of ART • Improve symptom free longevity by maximal, sustainable & durable suppression of viral replication (<50 copies/ml)

  36. Protocol for ART regimen • Confirmation of HIV diagnosis • Counseling for ART • Baseline investigations • Indications of therapy • Selection of regimens • Monitoring of ART • Switching of regimens • Resistance testing

  37. Confirmation of HIV diagnosis • Asymptomatic : Double ELISA • In Symptomatics with clinical marker of HIV/AIDS : Single ELISA • In Peadiatrics : ELISA, p-24, RT- PCR, Viral culture.

  38. Laboratory Test in HIV Monitoring • CD4 Count • Viral Load Viral Load and confirmation • HIV DNA PCR • HIV Culture • Quantitative RT-PCR Screening Test • Elisa/RIA • Rapid HIV Test Confirmatory test • Western Blot • Immunoflorescence IFA Resistant testing • Genotyping • Phenotyping

  39. Counselling for ART • Permanency of therapy • Cost of ART • Side-effects of ART • Adherence & compliance • Failure of therapy • Extended counseling for relatives & friends • Safe sex-practices

  40. Baseline investigations To Rule Out Underlying O.Is • X-ray chest • Montoux test • Sputum for AFB • USG abdomen • FNAC/Biopsy of lymphnodes • VDRL • HbsAg

  41. Baseline investigations • Prognostic Investigations • CD4 lymphocyte enumeration • Plasma Viral load • assays For Monitoring ARV • Hb • CBC • LFT • RFT • Blood sugar • Urine & Stool • S. Cholesterol • S.Triglycerides • S. Uric acid • S.Creatinine • S. Lactic acid • S. Amylase

  42. When to initiate ART? New insights: Changing Guidelines • Early’90s: HIV +ve? • 1998 CD4 count<500 • 2001 Cd4 count 200-350

  43. Indications of ART • AIDS defining HIV illness regardless of CD4 count and viral load levels - eg. esophageal candidiasis • CD4 counts < 200; Viral load > 1,00,000 copies/ml • Total lymphocyte count < 1200 cells/ml

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