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Transmission and Prevention of Transmission of HIV-1

Epidemic Spread of Disease. Ro = bDCWhen Ro >1 epidemic is sustainedb = Efficiency of transmission (

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Transmission and Prevention of Transmission of HIV-1

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    1. Transmission and Prevention of Transmission of HIV-1 Myron S. Cohen, MD J. Herbert Bate Professor of Medicine, Microbiology and Public Health The University of North Carolina at Chapel Hill

    2. 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

    3. 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

    5. Routes of Exposure and HIV 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 PEP1 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

    6. Amplified Transmission of HIV-1

    7. Acute HIV-1 Infection

    9. Four Prevention Opportunities Vaccine neutr antibodies Vaccine neutr antibodies

    10. Why Should Circumcision Prevent HIV Acquisition?

    11. Impact of MC on HIV: Evidence from Observational Studies and RCTs

    12. Four Prevention Opportunities Vaccine neutr antibodies Vaccine neutr antibodies

    13. Strategies for an HIV Vaccine

    15. ART to Prevent Sexual Transmission of HIV Post-exposure prophylaxis (PEP) Pre-exposure prophylaxis (PrEP) Treatment of the infected person

    16. nPEP US Guidelines A clinical trial to PROVE that nPEP works cannot be developed, but animals are protected With the availability of ART, nPEP usage became very commonand erratic with failures A CDC Advisory Committee helped generate guidelines MMWR Jan 21, 2005 Vol 54: 1-20 Antiretroviral Postexposure Prophylaxis After Sexual, Injection-Drug Use, or Other Nonoccupational Exposure to HIV in the United States

    17. Topical ART for HIV-1 Prevention

    18. HIV infection rates in the tenofovir and placebo gel groups: Kaplan-Meier survival probability

    20. iPrEX: Results HIV incidence: 2.1 per 100 py in FTC/TDF arm 3.9 per 100 py in placebo arm Reduction in HIV incidence: 44% overall, 73% in high adherers In FTC/TDF arm, drug detected in 51% of HIV seronegatives and in 9% of HIV seropositives, (P<0.001) More nausea in FTC/TDF arm in first 4 weeks; no difference in serious adverse events

    21. Four Prevention Opportunities Vaccine neutr antibodies Vaccine neutr antibodies

    22. Treatment as Prevention The Four Questions How effective are ART drugs to prevent HIV transmission? AND HOW WILL WE MAKE THEM MORE EFFECTIVE? What do we tell couples and infected people? -THE SWISS STATEMENT and its consequences Can we expect reduced population HIV incidence from ART? -Can this be measured and monitored? What are barriers to Treatment as Prevention? -Linkage to care -Adherence to ART (and which ART?) -HIV resistance (reflecting drug selection and adherence) -Acute, early infection and/or high viral load

    23. Treatment as Prevention Discordant Couples? POSITIVE RESULTS: Bunnell (JAIDS, 2007) Sullivan (IAS 2008) Donnell (Lancet, 2010) Romero (BMJ, 2010) NEGATIVE RESULTS: Wang (IAS, JAIDS, 2010)

    24. ART for Prevention: Assumptions=Results Cohen and Gay, CID 2010 An extensive group of mathematical modeling studies have examined the public health impact of ART for HIV prevention. The results have been mixed. Several studies, such as those of Blower et al and Lima et al, have suggested that widespread ART use could substantially reduce HIV incidence. However, other studies, such as those of Law et al, Fraser et al, and Wilson et al, have concluded that behavioral disinhibition could limit the preventive benefit of ART. Baggaley and colleagues concluded that ART is unlikely to reduce HIV transmission, due to the limited ability of ART to prevent HIV transmission, widespread emergence of ART resistance, and significant increases in risk-taking behavior. However, in a more utopian model, Granich et al argued that the HIV epidemic in Africa could be ended with universal annual HIV testing and immediate treatment. An extensive group of mathematical modeling studies have examined the public health impact of ART for HIV prevention. The results have been mixed. Several studies, such as those of Blower et al and Lima et al, have suggested that widespread ART use could substantially reduce HIV incidence. However, other studies, such as those of Law et al, Fraser et al, and Wilson et al, have concluded that behavioral disinhibition could limit the preventive benefit of ART. Baggaley and colleagues concluded that ART is unlikely to reduce HIV transmission, due to the limited ability of ART to prevent HIV transmission, widespread emergence of ART resistance, and significant increases in risk-taking behavior. However, in a more utopian model, Granich et al argued that the HIV epidemic in Africa could be ended with universal annual HIV testing and immediate treatment.

    25. Ecological Studies and ART Apparent benefit: San Francisco (PloS One, 2010) British Columbia (Lancet, 2010) No apparent benefit: Letters to Lancet Amsterdam France Australia The measurement of an ecological effect is extremely difficult BECAUSE introduction of ART with benefit does not construe causation

    26. HPTN 052 As part of our ongoing deliberations we designed a study for RRS that could be used as the basis for statistical simulations to further address the feasibility of conducting a trial in RRS. This slide outlines the proposed trial, similar in initial design to a composite of the two trials proposed by the INSIGHT network. As part of our ongoing deliberations we designed a study for RRS that could be used as the basis for statistical simulations to further address the feasibility of conducting a trial in RRS. This slide outlines the proposed trial, similar in initial design to a composite of the two trials proposed by the INSIGHT network.

    27. Treatment as Prevention The Test and Treat Movement THE HORSE IS OUT OF THE BARN Botswana cohort study (Essex) US HPTN 062 in NYC, DC, (El-Sadr, Mayer) Population ART in Tanzania (Fiddler, Hayes) HPTN 064, Africa (Hodder and others) Kisumu Kenya (Little) ANRS (Dabas and others)

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