Human Immunodeficiency Virus: An Overview

1. Human Immunodeficiency Virus: An Overview Elizabeth W. Delamater, Ph.D. Manager, Microbiological Sciences Division Laboratory Services Section Texas Department of State Health Services

2. HIV-1 HTLV-I HIV-2 HTLV-II (SIV) (STLV-I) Common Ancestor Transforming Viruses Cell Proliferation Cytopathic Viruses Cell Death

3. Human Retroviruses - Nomenclature • Human Immunodeficiency Viruses • HIV-1 (1983) • HIV, HTLV III, LAV, ARV • AIDS and related conditions • HIV-2 (1986) • LAV-2, HTLV IV • AIDS (primarily in West Africa)

4. Human Retrovirus – Characteristics • RNA Tumor (transforming) and immunodeficiency (cytopathic) viruses • Reverse Transcriptase • Integration of the viral genome into the host DNA as a provirus • Primarily infect T-lymphocytes and some neural cells • Exogenous (transmisssible, infectious agents) • Latency (long incubation period)

5. Brief History of Retroviruses • Transmissible agents capable of causing leukemias and solid-tissue tumors were discovered • 1970 – Reverse transcriptase was discovered • 1980 – HTLV-I and HTLV-II were isolated • 1981 – First AIDS case was discovered • 1983 – HIV-1 was isolated • 1985 – EIA test for anti-HIV-1 antibodies was licensed by the FDA

6. Where did HIV come from? • Estimated origin around 1930. • Estimated origin in Africa. • Thought to come from SIV in primates (blood exposure) • Change in travel and social norms caused the world wide epidemic.

10. HIV Subtypes • HIV isolates are classified into three different groups • Major group (M) • Outlier group (O) • Non-M / non-O (N) • Groups N and O restricted to West Africa • Based on the analysis of the envelope gene, there are at least nine pure subtypes or clades A-D, F-H, J and K

13. HIV Transmission Requires: 1) Infected body fluid. 2) Entry into the body. Blood, Semen, Vaginal Secretions & Breast Milk Mucous Membrane--Anal, Oral or Vaginal Sex Blood to Blood--Needle or Broken Skin Perinatal- In utero, During birth, Breastfeeding

14. Sexual Exposure to blood Perinatal Homosexual between men Heterosexual from men to women and women to men Drug user needle sharing Transfusion of blood, plasma Occupational needlestick injury and other blood exposures During pregnancy, intrapartum and postpartum (via breastfeeding) Routes of Transmission of HIV

15. Perinatal transmission • Greatly reduced due to use of antiretroviral therapy during pregnancy • decrease from 24 to 8% vertical transmission with AZT • Trials using high doses of new antiretrovirals during labor and to newborn--success of Nevirapine • Women with higher viral loads more likely to transmit

16. Factors Affecting Transmission STD Co-infection More likely to become infected More likely to transmit infection Viral Load Stage of infection Treatment

17. Disease Progression • Infection • Primary Infection/Antibody Development • Asymptomatic Period (10-12 yrs average) • AIDS (Opportunistic infections, CD4 200 or below)

19. AIDS HIV infected + immune system breakdown (CD4 count < 200 or AIDS Defining illness) AIDS Defining Illnesses Pnuemocystis pnuemonia Toxoplasmosis Kaposi’s sarcoma Mycobacterium avium complex Invasive cervical cancer etc...

20. Antiretroviral Treatment Triple Drug Cocktail--Attack the virus at different points in the replication process • Difficult Drug Regimens • Importance of Adherence • Side Effects • Expensive

22. Other Treatment Prophylaxis for Opportunistic Infections Treatment of Opportunistic Infections Vaccines (future) Immune Therapy Alternative Treatment

23. Difficulties in Treatment • Access to Care • Family Care Burdens • Language Barriers • Fragmentation of Care • Fears / Myths About Medical Care

24. Post Exposure Prophylaxis • Treatment with antiretroviral drugs after an exposure to HIV. • Must be started within 72 hours (sooner the better) and continued for a month. • PEP showed a 80% reduction in HIV infections for occupational exposures. • Concerns for drug and sexual exposures

25. 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 Estimated Number of AIDS Cases, Deaths, and Persons Living with AIDS,1985-2004, United States 450 90 AIDS 1993 definition implementation 400 Deaths 80 Prevalence 350 70 300 60 No. of cases and deaths (in thousands) 250 50 Prevalence (in thousands) 200 40 150 30 20 100 10 50 0 0 Year of diagnosis or death Note. Data adjusted for reporting delays.

26. Awareness of HIV Status among Persons with HIV, United States Number HIV infected 1,039,000 – 1,185,000 Number unaware of their HIV infection 252,000 - 312,000 (24%-27%) Estimated new infections 40,000 annually Glynn M, Rhodes P. 2005 HIV Prevention Conference

27. Awareness of Serostatus Among People with HIV and Estimates of Transmission ~25% Unaware of Infection Accounting for: ~54% of New Infections Marks, et al AIDS 2006;20:1447-50 ~75% Aware of Infection ~46% of New Infections People Living with HIV/AIDS: 1,039,000-1,185,000 New Sexual Infections Each Year: ~32,000

28. HIV/AIDS Diagnoses among Adults and Adolescents, by Transmission Category — 33 States, 2001–2004 MSM/IDU 5% Other 1% Other 3% Heterosexual 17% IDU 21% MSM 61% IDU 16% Heterosexual 76% Females (n ≈ 45,000) Males (n ≈ 112,000) MMWR, Nov 18, 2005

31. USA • Numbers of AIDS deaths are falling • Number of AIDS diagnosis are falling • Rates of HIV infection have NOT changed • Trends • Younger People (25% under age 25) • Low Socioeconomic Status • IDU • Disease of the Marginalized

32. Knowing You Are Infected: • Primary Infection • 2-6 wks average • 75 -90% have symptoms • Only way to know for sure: HIV Antibody Test “Window Period”: time to develop antibodies • 3-6 weeks 85% • 3 months >99%

33. Technologies More accurate serum EIA Oral fluids test Home test system Rapid test Urine test Strategies Phone results Augmented counseling Outreach Bars, coffee shops, bath houses Syringe exchanges Street (vans) Testing Technology

34. TDH HIV-1 Testing Algorithm Patient Specimen – EIA Screen Nonreactive Reactive Repeat screen 2X No further Testing Report as Nonreactive Reactive Nonreactive Nonreactive 2X Reactive 2X No further Testing Report as Nonreactive Western Blot Confirmation Reactive Indeterminate Nonreactive Retest 8 weeks Report Reactive Report Nonreactive

35. HIV ScreeningEnzyme ImmunoassayEIA or ELISA

36. EIA or ELISAAdvantages • Simple • Sensitive • Rapid • Can be Automated • Suitable for High Volume Testing

37. EIA or ELISALimitations • Potential for False Positives • Initial High Reactives must be Repeated

38. Types of Specimens for Testing Serum or Plasma

39. Plate with Antigen coated wells Add patient serum sample containing anti-HIV-1 antibodies Wash, add enzyme conjugated anti-human antibodies

40. Wash, add appropriate substrate for the conjugated enzyme Enzyme acts on substrate, causing a color change

49. Types of Specimens for Testing Serum or Plasma Dried Blood Spots