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The HIV Pandemic 2008 Where Do We Go From Here?

The HIV Pandemic 2008 Where Do We Go From Here?. Myron S. Cohen, MD J. Herbert Bate Professor Medicine, Microbiology, Public Health Director, UNC Institute of Global Health The University of North Carolina-CH. Critical Issues in HIV. The Pandemic Global Treatment Prevention

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The HIV Pandemic 2008 Where Do We Go From Here?

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  1. The HIV Pandemic 2008Where Do We Go From Here? Myron S. Cohen, MD J. Herbert Bate Professor Medicine, Microbiology, Public Health Director, UNC Institute of Global Health The University of North Carolina-CH

  2. Critical Issues in HIV • The Pandemic • Global Treatment • Prevention …and UNCs role

  3. The beginning …

  4. Hubei Medical College, 1979 Me

  5. A global view of HIV infection 38.6 million people [33.4‒46.0 million] living with HIV, 2005 2.4

  6. Where is HIV Going Next? • HIV is STAYING in Africa • India • China • Russia • ????

  7. About 14,000 new HIV infections daily • >95% new infections in developing countries. • 2,000 in children under 15 years of age. • 12,000 are in people aged 15-49 years • * about 50% are 15–24 year olds. • * almost 50% are in women • 4 new people infected for every person treated!

  8. Epidemic Spread of Disease Ro = bDC When Ro >1 epidemic is sustained b = Efficiency of transmission (…a biological event) D = Duration of infectiousness C = Number of people (partners) exposed

  9. Transmission of Infectious Diseases:Biological Requirements Infectious Susceptibility Inoculum (concentration) Hereditary resistance Phenotypic factors Innate resistance Acquired (immune) resistance *communicability and virulence are two different concepts

  10. Routes of Exposure and H.I.V. INFECTION ROUTE RISK OF INFECTION Sexual Transmission a. Female-to-male transmission………..1 in 700 to 1 in 3,000 b. Male-to-female transmission……...….1 in 200 to 1 in 2,000 • Male-to-male transmission………...….1 in 10 to 1 in 1,600 • Fellatio??…………………………….. 0 (CDC) or 6% (SF) Parenteral transmission • Transfusion of infected blood………….95 in 100 • Needle sharing………………………….1 in 150 c. Needle stick…………………………..…1 in 200 d. Needle stick /AZT PEP…………………1 in 10,000 Transmission from mother to infant a. Without AZT treatment………...…….1 in 4 b. With AZT treatment………………….Less than 1 in 10 Royce, Sena, Cates and Cohen, NEJM 336:1072-1078, 1997

  11. Coital Frequency per Month by Age 11 10.02 10 9.11 8.98 9 8 Coital frequency per Month 7.44 7 6 5 4 15-24 25-29 30-34 35-59 Age

  12. Hypothesis 1) Estimated transmission rates are too low to explain the epidemic 2) HIV transmission is intermittently AMPLIFIED by increased genital tract shedding 3) AMPLIFIED transmission is critical to the spread of HIV 4) OTHER Sexually Transmitted diseases play a key role

  13. Biological Determinants That Affect HIV Sexual Transmission InfectiousnessLevel of Blood Viral LoadGenital Viral LoadStage of InfectionGenital ulcerations Inflammatory STDsCervical ectopyViral Subtype X4/R5 PhenotypeHormonal contraception Acquisition Genital ulcers Inflammatory STDs Cervical ectopy HLA Haplotype Chemokines/Cytokines Hormonal contraception Lack of Circumcision

  14. 6 4 2 0 AIDS Acute Infection 3 wks Asymptomatic Infection HIV Progression Big Idea I: Transmission in Clusters Risk of Transmission Reflects Genital Viral Burden 1/30- 1/70 HIV RNA in Semen (Log10 copies/ml) 1/100- 1/1000 1/500 - 1/2000 1/1000 - 1/10,000

  15. 5 4 3 2 Acute HIV Infection & STD Coinfection AIDS STD Episode STD Episode Big Idea II: “Classical” STDs Drive HIV 1/30 or greater odds of transmission to a susceptible partner per coital act HIV RNA in Semen (Log10 copies/ml)

  16. Differential Diagnosisof Genital Ulcer Disease

  17. "The Tip of the Iceberg" Recognized infection 9.2% 90.8% Unrecognized and asymptomatic infection Iceberg represents all those withHSV-2 antibody

  18. UNC Global Health Research Sites“TO BE AND NOT TO SEEM”

  19. Malawi Overview • Population 10 million • 90% rural • Per Capita income $190 AIDS impact • 900,000 people living with HIV • 15% adult prevalence • STD Clinic: 47% prevalence

  20. HIV-1 Viremia and SheddingPilcher et al. AIDS, 2007

  21. Projected life expectancy in 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

  22. In 9 Sub-Saharan African countries, one-fifth to one-third of all children under the age of 15 Were orphaned by the year 2000 US Census Bureau

  23. AIDS Mortality Rates: 1996-2001 Mortality vs ART utilization 100 40 Percentage of Patient-days on HAART 35 USE OF ART 30 75 25 DEATHS Percentage of patient-days on ART 20 50 Deaths per 100 person-years 15 10 25 Deaths per 100 Person-Years 5 0 0 1995 1996 1997 1998 1999 2000 2001 Palella F, et al. 2001; 8th CROI. Abstract 268b.

  24. ART Access June 2006 UNAIDS, 2006

  25. Presidential Emergency Plan for AIDS Relief (PEPFAR) • 15 “focus” countries…(but funds in > 120) • Trained lab personnel, counselors, infrastructure, distribution/management of ART and other drugs • Care provided to 3,000,000 people • >600,000 provided ART • $15,000,000,000 over 5 years (maybe more!) ….and The Global Program, Three x Five and others! As of 2007…THE US IS PRIVIDING 1/3 of ALL PLANETARY HIV TREATMENT AND CARE

  26. Opportunities to Prevent HIV 1) BEFFORE EXPOSURE 2) AT EXPOSURE (PrEP) 3) AFTER EXPOSURE (PEP) 4) SECONDARY TRANSMISSION “positive prevention”

  27. Prevention of HIV • STD control, behavior change, condom • Topical microbicides (Trials ongoing) • The diaphragm (Trial completed!) • Male circumcision (Trials completed!) • Antiviral therapy (Trials ongoing) - for HIV (treat both HIV+ or HIV-) - for HSV to prevent HIV (treat HIV+ or-) • Societal (Structural) Change: Incentives for safer sex, needle exchange?

  28. Vaccines for Prevention of HIV Infection Good News: HIV proteins are immunogenic Animal success stories with clues to immunity Bad News: No reliable surrogates of immunity Short-lived immunity VAXGEN Failure Merck 502,503 Failure (Sept 22,2007)!!! The Cost : Benefit ratio-Disinhibition

  29. Potential end-points of HIV-vaccine efficacy trials protection against HIV sterilizing immunity protection against disease (modification of the course of HIV infection in vaccine recipients) no protection establishment of chronic infection with low viral load “normal” infection with variable levels of viral load initial infection “controlled” no infection UNAIDS–97100 1 August 1998

  30. Merck 502 • AD5, HIV CTL stimulation, no envelope • Study stopped in September 2007 for FUTILITY!! • No protection from HIV acquisition • No reduction in viral load set point WHATS NEXT?????

  31. This CHAVI web site is at http://www.chavi.org

  32. Relationship Between HIV and Male Circumcision HIV Seroprevalence (%) % Circumcised males Bongaarts AIDS 1989

  33. Possible circumcision protective mechanisms Anatomiceffect by removal of foreskin Circumcision Reduced GUD, reduced cofactor effects Reduced Target cells for HIV

  34. 15 Overall 58 ( 66, 48) Impact of MC on HIV : Evidence from observational studies and RCTs Reduction of risk (95% CI) Weiss et al. AIDS 2000, 14:2361-70 7 1 Auvert et al. PLoS Med 2005(11): e298.2006 South Africa (RCT) 60 ( 76, 33) 1 Bailey et al. Lancet 2007; 369: 643–56 59 ( 76, 30) Kenya (RCT) 1 Gray et al. Lancet, 2007, 657–66 51 ( 82, 14) Uganda (RCT) 60 85 80 70 .50 1 Reduction of risk (0%)

  35. Modeling the Impact of Circumcision on HIV Prevalence/Incidence • In SSA, 100% uptake of MC could avert 2 million new infections and 300,000 deaths over ten years • In Soweto, 50% uptake of MC could avert 32,000 – 53,000 new infections over 20 years • Prevalence would decline from 23% to 14% …BUT, Can we really CIRCUMCIZE our way out of the HIV pandemic??? Sources: Williams et al., 2006; Mesesan et al., 2006

  36. Antiretroviral Therapy Effect on HIV Transmission ?

  37. Topical Microbicides –Current Products BufferGel SAVVY Pro2000 Cellulose Sulfate PMPA/ Tenofovir

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