1. P1 Virology, Pathogenesis And Treatment Of HIV Infection

2. P2 Learning Objectives The LT will know what is HIV and the disease burden caused by it? What is AIDS? How it is acquired? How it establishes in body? How to prevent getting infected with HIV? How HIV causes disease? How the HIV disease progresses (natural history)? How the body fights the virus ? Role of CD4 cells What effects are produced in the body? How the patient is treated? What is ART?

3. P3 HIV and AIDS HIV HIV is human immunodeficiency virus. Two types HIV 1 and HIV 2 Both have many subtypes AIDS Acquired immune deficiency syndrome- Last stage-HIV disease- CD4 cells less than 200/µ L And patient sick with opportunistic infections.

4. P4 Disease burden due to HIV There are 33 million HIV infected allover the world. 2.3 to 2.5 million of these are in India Prevalence of HIV 0.36% in general population amongst people like you and me. Prevalence is higher in high risk groups (CSW,MSM, IDUs, STI cases, migrants, etc where 5-10-20 or more out of 100 may have HIV) NACP III extremely important to provide care, support, and treatment to HIV positive and prevent new HIV infections

5. P5 5 Structure of HIV

6. P6 1. Sexual Transmission (vaginal, anal, oral) Heterosexual (most common in India) Homosexual 2. Blood Contact Blood and blood products transfusions Intravenous drug use Occupational exposure (needle stick, cuts etc.) 3. Mother-to-Child During pregnancy During delivery Breast Feeding Routes/Mechanisms of Transmission

7. P7 Sexual Transmission: Safe sexual practices, using condoms etc. Transmission through blood and blood products: Ensure screened blood and blood products are used (Safe blood and blood products, rationale use of blood) Through needles (IDUs), needle stick and occupational exposure: standard work precautions and PEP (safe needles including for IDUs) HIV positive mother to the baby: PPTCT program Prevention of HIV Transmission

8. P8 Susceptibility of HIV HIV is a highly fragile virus. Needs living cells to survive. The methods used for sterilization and disinfection to kill the virus. Autoclaving at 121 0 C at 15 lb pressure for 20 minutes Dry heat 160 0 C for 1 hr. (holding time) Boiling for 20 minutes Sodium hypochlorite 1% (routine) 10% (spill) Ethanol 70% Povidone iodine (PVI) – 10% Glutaraldehyde (activated) 2% for 30 minutes 8

9. P9 9 HIV Pathophysiology - Life Cycle CD4 cell

10. P10 Step One: Attachment

11. P11 11 HIV Pathophysiology - Life Cycle CD4 Co-receptor (CCR5 or CXCR4) CD4 Binding

12. P12 HIV Pathophysiology - Life Cycle FUSION

13. P13 HIV Pathophysiology - Life Cycle Virion entry

14. P14 HIV Pathophysiology - Life Cycle HIV RNA

15. P15 HIV Pathophysiology - Life Cycle Reverse transcription HIV DNA

16. P16 HIV Pathophysiology - Life Cycle Translocation to nucleus

17. P17 HIV Pathophysiology - Life Cycle Integration

18. P18 HIV Pathophysiology - Life Cycle Transcription / Translation of HIV mRNA / polyprotein

19. P19 HIV Pathophysiology - Life Cycle Protease processing and viral assembly

20. P20 Normal Defense Of Body And Host Response To HIV Infection (Natural History Of HIV Infection)

21. P21 lymphocytes neutrophils monocytes eosinophils basophils erythrocytes platelets Various Blood Components

22. P22 Normal body defenses and HIV The body’s normal defenses are: B cell: humoral immunity antibodies T Cell population: CMI - CD4 – helper T CD8 – cytolytic T cell HIV targets these defenses, primarily attacking CD4 cells. CD4 cells are progressively lost during the course HIV disease (in the absence of treatment) leading to continuous viral replication and increased opportunistic infections.

23. P23 Window period Time taken from day of HIV infection to positive HIV antibody test (ELISA/RAPID) Most HIV infected seroconvert within six months

24. P24 24 AIDS Clinical latency Acute HIV Infection Natural History of HIV-1 Infection Progressing to AIDS* 1-12 weeks6-10 years 1-2 years Viral Load CD4 cell level Acute HIV infection Clinical latency AIDS 6-12weeks 6-11 years 1-2 years *Without ART

25. P25 25

26. P26 Rate of progression of HIV infection without ART Based on kinetics of virologic and immunologic events three dominant patterns of HIV disease are described. 1.80-90% of HIV infected are typical progressors survival time appx. 11 years. 2.5-10 are “rapid progressors” with median survival time of 3-4 years. 3.7-10% of HIV-infected individuals do not experience disease progression for extended period of time and are called “long term non progressors” (LTNPs).

27. P27 Life Cycle and ARVs site of action Reverse Transcriptase Inhibitors (12) Protease Inhibitors (7) Fusion/Entry Inhibitors (1) Integration Inhibitors

28. P28 ART works: Progression to AIDS/Death 30 20 1010 5 0 25 15 1 2 3 4 5 6 7 8 9 10 11 12 13 No Therapy Mono- Therapy Dual Therapy Triple Therapy Months % Patients Progressing JAMA 1998