HIV & AIDS

1. HIV & AIDS BY DR MAHESH MATHUR,MD,DCP DERMATOLOGIST CMS

2. WHY SHOULD WE KNOW ABOUT THIS DISEASE ?

3. 25 yars of pandemic of HIV • In July 1981 – Birth Year of HIV/AIDS • -Lawrence Altman in the New York times • Dec.1982 Epidemic in MSM • In 1984 –The Agent- retrovirus-HTLV III • Renamed in 1986 HIV & serological tests • In 1987 –Zidovudine • Since 1996- HAART –Dramatic decrease in Mortality

4. Epidemiology • 41 million people are infected with HIV world wide (UNAIDS) • >70% Reside in Sub- Saharan Africa; • App. 16000 New infection occurs Daily, Majority Young adults. • HIV is Leading single cause of Death in young. • 500 Young adults & 1000 Children dieing every day

6. Estimated number people living with HIV in Asia, 1990–2007 7 6 Millions 5 4 3 2 1 0 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 Year This bar indicates the range

8. Virology HIV-1 and the less common HIV-2 belong to the lentivirus group of virus of the family retroviruse. • HIV-1 contains a single-stranded RNA genome -9 genes that encode 15 different proteins. • The major viral proteins are • structural proteins (Gag, Pol, and Env), • Regulatory proteins (Tat and Rev), • Accessory proteins (Vpu, Vpr, Vif, and Nef). • Three major classes of HIV-1 • M (main), 90% • N (new), and • O (outlier).

9. THE VIRUS -gp120 -gp 41 -P24

10. SERO TYPES OF HIV

11. The Role of Host-Virus Factors in Infection • Three components of the host-virus interaction. • The virus itself - Viral strains lacking nef sequences do not produce AIDS in their hosts.(Australian cohort) • Innate host factors are important in containing infection. CCR5,CXCR4 the "second receptor" on CD4 T cells • The humoral and cellular arms of immune system . Humoral responses -detectable one to six months following infection. • The viremia of acute infection is controlled by cytotoxic T lymphocytes

12. Host Immune Responses & IMMUNE Pathogenesis • Cellular immunity • CD4 helper T cells. • The characteristic quantitative & qualitative depletion of CD4+ T lymphocytes in HIV, • Cellular destruction, • Diminished cellular production, • Cellular sequestration in lymphoid organs • CD8 T lymphocytes (CTLs)- kill HIV-infected cells - immune mechanism regulating HIV replication

13. TRANSMISSION OF HIV • SEXUAL CONTACT–53% HOMO & HETERO SEXUAL CONTACT • PERINATAL TRANSISSION –15 to 40 % • TRANS PLACENTAL 70% of infection • DURING DELIVERY THROUGH INFECTED BIRTH CANAL 10 to 15 % • AS A RESULT OF INGESTION OF BREAST MILK CARRYING VIRUS 15% • TRANSFUSION OF BLOOD,BLOOD PRODUCTS & ORGEN DONATION • CONTAMINATED NEEDLES • HEALTHCARE WORKERS HAVE A RISK OF APP. 0.3% FOLLOWING A SINGLE NEEDLE-STICK INJURY WITH KNOWN HIV INFECTED BLOOD • ACCIDENTAL INOCULATION ~0.09%

14. PATHOGENESIS

15. AIDS DEFINITION 1993 • CLINICAL CATEGORIES • A – ADULT/ADOLESENT >13 YEARS WITH DOCUMENTED HIV INFECTION & CONDITIONS LISTED IN B&C NOT PRESENT • B – CONDITIONS ATTRIBUTED TO HIV INFECTION ORINDICATIVE OF DEFECT IN CMI AND PHYSICINE CONSIDERING HIV INFECTION IN MANAGEMENT OF DISEASES • C- AIDS DEFINING CONDITIONS

16. CDC CLASSIFICATION OF HIV 1993

17. A diagnosis of AIDS is made whenever a person >13 years age is HIV positive and: • He or she has a CD4+ cell count <200 cells/µL, or • His or her CD4+ cells account for <14% of all lymphocytes, or • That person has been diagnosed with one or more of the AIDS-defining illnesses listed below.

18. CLINICAL COURSE OF DISEASE

19. Frequency of Symptoms associated with Acute retroviral syndrome

20. MUCOCUTANEOUS LESIONS • Cutaneous infection associated with HIV/AIDS • Viral- HSV, VzV, Molluscum Contagiosum • Bacterial – Staphylococcus, Bacillary Angiomatosis,Mycobacteria • Fungal – Candidia,Dermatophytosis Penicillium • Parasitic infection - Scabies • Inflammatory Non infectious Dermatosis • Eosinophilic Folliculitis • Seborrheic Dermatitis • Pruritus • psoriasis • Adverse Cutaneous Drug eruptions • HIV & Skin Cancers

21. MOLLUSCUM CONTAGIOSUM

22. HERPES SIMPLEX

23. HERPES SIMPLEX

24. HERPES ZOSTER

25. HERPES ZOSTER

26. VIRAL WARTS

27. HAIRY LEUCOPLAKIA

28. ORAL CANDIDIASIS

29. SCABIES

30. KAOSI’S SARCOMA 1872

31. DRUG RASH

32. EOSINOPHILIC FOLLICULITS

33. Seborrhoic Dermatitis

34. LABORATORY INVESTIGATIONS -Screen blood -Diagnose infection, -Monitor disease progression in individuals infected by HIV. 1) Detect antibody, 2) Identify antigen, 3) Detect or monitor viral nucleic acids, and 4) Estimate of CD 4 +T-lymphocyte

35. HIV Screening Antibody tests - ELISA TEST FOR HIV-1 & 2 (gp120,41) >99.5% SENSITVITY FALSE POSITIVE OCCURS IN HEPATIC DISEASE ACUTE VIRAL INFECTIN RECENT VIRAL VACCINATION AUTOANTBODIES

36. The HIV Antigen Test The p24 antigen assay The viral (core) p24 protein in blood, Detectable earlier than HIV antibody during acute infection. -Highly specific with high levels of viremia during which the individual is highly infectious. PCR - 99.9%. Testing is of value in: -detecting early HIV infection, -screening blood, -diagnosing infection in the newborn, -monitoring antiviral therapy. • VIRAL RNA TEST • RT-PCR • bDNA • NASBA -

37. APPROCH TO INVESTIGATION

38. Introduction to HAART • Where it has succeeded, • Highly Active Antiretroviral Therapy (HAART)has altered the nature of HIV disease, • Transforming an almost uniformly fatal illness into a chronic but apparently stable tratable condition.

39. ANTIRETROVIRAL Drug Classes • There are currently 5 major classes of antiretroviral drugs in general use: • Nucleoside analogue reverse transcriptase inhibitors (NRTIs), • Nonnucleoside reverse transcriptase inhibitors (NNRTIs), • Protease inhibitors (PIs), • Fusion inhibitors. • Integrase Inhibitors

40. Nucleoside analogue reverse transcriptase inhibitors (NRTIs) • NRTIs -Inhibit the synthesis of DNA by reverse transcriptase, enzyme that copies viral RNA into DNA in the newly infected cell. • Reverse transcriptase fails to distinguish the phosphorylated NRTIs from their natural counterparts & use the drugs in the synthesis of viral DNA. • When an NRTI is incorporated into a strand of DNA being synthesized, the addition of further nucleotides is prevented, and a full-length copy of the viral DNA is not produced. • ZIDOVUDIN,DIDANSINE,LAMIVUDIN ZALCITABIN

41. Nonnucleoside reverse transcriptase inhibitors (NNRTIs) • NNRTIs also inhibit the synthesis of viral DNA, but rather than acting as false nucleotides, • the NNRTIs bind to reverse transcriptase in a way that inhibits the enzyme's activity. • DELAVIRDINE,EFAVIRENZ,NEVIRAPIN

42. Protease inhibitors (PIs) • PIs bind to the active site of the viral protease enzyme, preventing the processing of viral proteins into functional forms. Viral particles are still produced when the protease is inhibited, but these particles are ineffective at infecting new cells. • INDINAVIR,RITONAVIRNELFINAVIR

43. Fusion inhibitors • Fusion inhibitors prevent HIV from entering target cells. • Drugs of this class bind to the HIV envelope protein gp41, which is involved in viral entry. • By blocking the interactions between regions of the gp41 molecule, fusion inhibitors interfere with the conformational change (folding) of the envelope molecule required for fusion with the target cell membrane. • ENFUVITIDE

44. ANTIRETROVIRAL Drug Classes

45. TREATMENT RECOMMENDATIONS (HAART)

46. SIDE-EFFECT OF ANTIRETROVIRAL DRUGS • Nucleoside/Nucleotide Analogues • HYPERSNSITIVITY REACTION • SKIN RASHES & SKIN PIGMENTATION • MITOCHONDRIAL DYSFUNCTION & LACTIC ACIDOSIS • MEGALOBLASTIC ANEMIA & MYELOSUPPRESSION • POLYNEUROPATHY WITH ZALCITABIN • NAIL PIGMENTATION WITH ZUDOVUDIN

47. Nonnucleoside Reverse Transcriptase Inhibitors • SKIN RASHES, SJ SYNDROME • HEPATOTOXICITY • CONTRAINDICATED IN PREGNANCY • PROTEASE INHIBITORS • ABNORMAL LIVER FUNCTION • BODY FAT REDISTRIBUTION • ABNORMAL PLASMA LIPIDS • HYPERGLYCEMIA & PANCREATITIS WITH RITONAVIR & SQUINAVIR • NEPHROLITHISIS WITH INDINAVIR

48. PREVENTION • The protection against exposure to HIV. • Antiretroviral therapy cannot replace behaviours that help avoid HIV exposure • sexual abstinence, • sex only in a mutually monogamous relationship with a noninfected partner, • consistent and correct condom use, • abstinence from injection-drug use, • consistent use of sterile equipment by those unable to cease injection-drug use). • Medical treatment after sexual, injection-drug--use, or other nonoccupational HIV exposure is less effective than preventing HIV infection by avoiding exposure

49. PROPHYLAXIS • Non occupational exposure • Any direct mucosal, percutaneous, or intravenous contact with potentially infectious body fluids that occurs outside perinatal or occupational situations e.g., health-care, sanitation, public safety, or laboratory employment. • Potentially infectious body fluids are blood, semen, vaginal secretions, rectal secretions, breast milk or other body fluid that is contaminated with visible blood • Antiretroviral therapy initiated as soon as possible within 48--72 hours of sexual, injection-drug--use, and other substantial nonoccupational HIV exposure

50. Recommendations for the prompt initiation of nPEP with HAART • when persons seek care within 72 hours after exposure, • The source is known to be HIV infected, and the exposure event presents a substantial risk for transmission. • When the HIV status of the source is not known and the patient seeks care within 72 hours after exposure, • PEP in not recommended for Kissing & other sexual contact without semen/blood mucosal contact • The diminished potential benefit of nPEP outweighs the potential risk for adverse events from antiretroviral medications.