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HIV & AIDS in the United States

HIV & AIDS in the United States. AIDS deaths in the U.S. decreased by 42% from 1996 - 97 >1,000,000 Men, Women & Children were living with HIV in 2004 >45,000 new infections in 2004 Women accounted for > 30% of new HIV diagnoses in adults. U.S. HIV & AIDS by Race/Ethnicity since 1999.

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HIV & AIDS in the United States

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  1. HIV & AIDS in the United States AIDS deaths in the U.S. decreased by 42% from 1996 - 97 >1,000,000 Men, Women & Children were living with HIV in 2004 >45,000 new infections in 2004 Women accounted for >30% of new HIV diagnoses in adults

  2. U.S. HIV & AIDS by Race/Ethnicity since 1999 Among new AIDS cases in men, 61% were in African Americans and Hispanics Among new AIDS cases in women, 80% were in African Americans and Hispanics AIDS is now the #1 killer of African American women age 25 - 34 HIV incidence among African Americans is now 8 times higher than among Caucasians

  3. U.S. versus GLOBAL HIV NUMBERS • HIV infection is more common than previously thought >40 million now HIV infected • 5 million infected in 2004 @ a rate of ~14,000/day ~ 2000 in children <15 y.o. ~ 12,000 in persons 15 - 49 y.o. (50% women; 50% 15 - 24 y.o.) •  1% of sexually active adults are infected •  90% of the infected don't know it! •  >3 million died from AIDS in 2004 • - 60% more than in 1996 • >33% were Adult women • ~20% were under 15 years old

  4. In Sub-Saharan Africa: 8% of 15-49 years old are infected  In Botswana, Zimbabwe, Nigeria, Swaziland 25 - 30% of adults are infected  In large towns of Zimbabwe ~70% of pregnant women are infected

  5. Causes of deaths, globally and in Africa 20 19 18 16 14 12 Global 10 Percent of deaths Africa 8 6 4.2 4 2.8 2.3 2.2 2 0.3 0 HIV/AIDS Tuberculosis Lung cancer

  6. Projected changes in life expectancy in selected African countries with high HIV prevalence, 1995–2000 65 60 55 50 45 40 35 Average life expectancy at birth, in years Botswana Zimbabwe Zambia Uganda Malawi 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 Source: United Nations Population Division, 1996

  7. HIV prevalence rate among teenagers in Kisumu, Kenya, by age 35 33.3 29.4 30 25 22 HIV prevalence (%) 20 17.9 boys girls 15 8.6 10 8.3 3.6 5 2.2 0 0 0 15 16 17 18 19 Age in years Source: National AIDS Programme, Kenya, and Population Council, 1999

  8. Much of what we took for granted has been proven wrong... despite the most concerted effort of medical research in modern history. e.g. - Exclusive CD4 cell tropism - Idea of viral dormancy etc. - Combination therapy

  9. CO-OPTION AND DESTRUCTION OF THE IMMUNE SYSTEM BY HIV

  10. OVERVIEW OF THE HIV LIFECYCLE

  11. OVERVIEW OF THE HIV LIFECYCLE

  12. CLINICAL COURSE OF HIV INFECTION

  13. Dynamics of CD4 cell Numbers during HIV Disease Surprising finding of very high rates of HIV replication & CD4 cell turnover in HIV+ patients Current estimates of 100 billion new HIV particles / day 1 - 2 billion CD4 cells are killed and regenerated / day

  14. ALTERNATIVE RECEPTORS FOR HIV (CD4-INDEPENDENT) CD4- cells can be infected by HIV e.g.: Bowel/Renal epithelia

  15. (1) GalC -Galactosyl ceramide • A glycolipid • may cluster with other glycolipids •  Form lipid rafts + CD4 • HIV infects cultured neuronal cell lines • anti-GalC Abs block in both CD4- cell lines  some accumulation on surface

  16. HIV CELL HSV pseudotypes (2) Pseudotype Viruses in HIV Infection • Formation of chimeric viruses where one viral genome can be encapsulated within a different viral envelope • - created in vitro by co-infection with two viruses • HIV pseudotypes observed include: • HIV-1 + HIV-2 • HIV-1 + HTLV-I • HIV + murine retroviruses • HIV + herpes viruses e.g. HSV

  17. gp120/41 CD4 DIRECT TOXIC EFFECTS OF HIV PROTEINS Primarily via changes in the cell membrane (a) Auto Fusion Evidence for a loss in osmotic balance  decrease in intracellular ionic strength  results in cell ballooning and lysis (b) Cultured brain cells exposed to gp120 show an influx of Ca2+  overactivation of Ca2+ Kinases etc.  Reversed by nimodipine - Ca channel antagonist

  18. HIV-induced Apoptosis via Fas Receptor The FasL/Fas (CD95) ligand/receptor complex helps maintain lymphocyte homeostasis via cell depletion

  19. Fas/FasL Mechanism of Action CAD (caspase-activatable DNase)

  20. Observation: uninfected T-cells from HIV+ Patients • Have a higher degree of activation • Have  Fas expression on their surface • Are more sensitive to FasL induction of apoptosis • HIV infection of macrophages/monocytes increases the production of FasL •  Uninfected T-cells undergo apoptosis when cocultured (Contact necessary)

  21. Human APCs, macrophages can produce FasL and are upregulated when HIV infected • This elevated level of FasL expression can induce apoptosis in uninfected T-cells (by contact) • IN THE CENTRAL NERVOUS SYSTEM • soluble FasL also detected in cerebrospinal fluid (CSF) samples from HIV-infected patients  may contribute to brain injury with progression to AIDS • specifically targets astrocytes and glial cells

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