1. Biomedical Approaches to HIV Prevention HIV Research Catalyst Forum April 21, 2010, Baltimore, MD Monica S. Ruiz, PhD, MPH George Washington University School of Public Health and Health Services

2. HIV Prevention Strategies Infected Person (transmission & disease progression) Susceptible Person (acquisition) Treatment of Addiction NEP/SEP PMTCT Microbicide Treatment of STD and OI Treatment of Addiction NEP/SEP STD Treatment PMTCT Microbicide VCT Behavioral Risk Reduction ART VCT Behavioral Risk Reduction Vaccine PEP PrEP Male Circumcision

3.  Decrease susceptibility to HIV by:  Reducing risk of exposure to the virus  If exposed, reduce risk of the virus “taking hold”  Decrease infectiousness of HIV by:  Reducing viral load  Reducing the other biological factors (e.g., infections) that increase transmission risk Biomedical & Technological Interventions

4.  Male, latex condoms are 80% to 95% effective in reducing the risk of HIV transmission when used consistently and correctly  Female condoms are estimated to be between 94% and 97% effective in reducing risk of STI, including HIV, transmission when used consistently and correctly Condoms References: NIH, 2001; Hearst & Chen 2003; Weller & Davis 2004; Holmes, et al. 2004; Trussell et al. 1994.

5.  Long- and short-course AZT and single-dose NVP are effective in reducing MTCT by 44% to 66%  Breast-milk substitutes have been shown to significantly reduce infection among infants.  The number of children who acquired HIV perinatally decreased by 89% between 1992 and 2001 Preventing Mother-to-Child Transmission Sources: Brocklehurst 2004; Cooper et al. 2002.

6. Male Circumcision Two meta-analyses of observational studies found the risk of acquiring HIV among circumcised men was about half that of uncircumcised men. Data from three RCTs showed that circumcision has a significant protective effect against HIV acquisition South Africa: 61% protective Kenya: 53% protective Uganda: 48% protective Sources: Weiss, et al. 2000; Siegfried, et al. 2004; Auvert, et al. 2005; Bailey et al., 2007; Gray et al., 2007

8. Cervical Barrier Methods  The cervix may be particularly vulnerable to HIV and STI transmission.  The MIRA trial found that there was no added protective benefit from the diaphragm.  But the trial was not designed to determine whether the use of the cervical barrier was better than nothing at all.  Other cervical barriers, when combined with an effective microbicide, may be more successful in preventing HIV infection Sources: Padian et al., 2007

9. HIV Lactobacillus Vaginal epithelium physical barrier lubrication Maintenance of normal microflora Viral disruption/inactivation Prevention of other STDs Microbicides

10. Microbicide Trial results to date Study NameSponsorPopulation Microbicide candidate(s) being tested Findings HPTN 035NIH 3,099 women from sites in Malawi, South Africa,US, Zambia and Zimbabwe. BufferGel & PRO 2000 30% efficacy for PRO 2000 (NS) No observed efficacy for BufferGel CarraguardPopulation Council, USAID, BMGF 6,202 women from 3 sites in South Africa CarraguardNo observed efficacy Cellulose Sulfate CONRAD, USAID, BMGF 1398 women from sites in African and India Cellulose Sulfate More observed infections in the CS group than placebo (NS) Trial stopped early for fear of harm

11. Vaccines

12. X X

15.  STIs increase susceptibility to HIV infection.  Having HSV-2 infection (genital herpes) is associated with 3x higher risk of HIV acquisition.  HSV-2 can also increase infectiousness of HIV+.  STI management may be most effective in populations with concentrated sexually transmitted HIV epidemics and in populations with high prevalence of STIs and sexual risk behaviors Treatment and Management of Sexually Transmitted Infections Freeman et al. 2006; Grosskurth et al. 1995; Wawer, et al 1999; Kamali, et al 2003; Korenromp et al. 2005. Sources: Freeman et al. 2006; Grosskurth et al. 1995; Wawer, et al 1999; Kamali, et al 2003; Korenromp et al. 2005.

16. HSV-2 Trial Results Two trials of HSV-2 treatment in HIV-uninfected persons showed no protective effect against HIV acquisition One trial of HSV-2 treatment among HIV+ persons showed no evidence of reducing rates of HIV transmission Mixed results re: the impact of HSV-2 treatment on genital HIV shedding, viral load levels, genital HSV shedding, etc.

17. Post-Exposure Prophylaxis (PEP) A short course of ART taken within 72 hours of exposure can be effective in preventing HIV infection A short course of ART taken within 72 hours of exposure can be effective in preventing HIV infection One study of occupational PEP found that AZT taken within 24 hrs. of exposure and over 28 days reduced HIV acquisition by 81% One study of occupational PEP found that AZT taken within 24 hrs. of exposure and over 28 days reduced HIV acquisition by 81% Cardo et al. 1997; Wulfsohn 2003; Mayer 2003. Sources: Cardo et al. 1997; Wulfsohn 2003; Mayer 2003.

18. Pre-Exposure Prophylaxis (PrEP)

19. Many difficult questions are associated with PrEP

20. Ongoing PrEP Trials Source: www.avac.org

22. Biomedical strategies are only one piece of the prevention puzzle Behavioral, social, and structural interventions are important too! It is not likely that any one intervention will be 100% effective. We must not confuse lack of implementation with lack of effectiveness. So what do we know?

23. Other important factors that must be considered in HIV prevention Psychological, social, economic, and cultural dynamics of gender and sexuality New and changing context for both sexual and substance use behavior Differences in the perceived consequences of HIV infection Social, structural, environmental factors and contexts that contribute to the HIV/AIDS epidemic

24. Infected Person (transmission & disease progression) Susceptible Person (acquisition) Rx Addiction NEP/SEP Perinatal Microbicide Rx HIV Rx STD Rx OI Rx Addiction NEP/SEP Rx STD Perinatal Microbicide VCT Behavioral Risk Reduction ART VCT Behavioral Risk Reduction Vaccine PEP/PREP Access to & Delivery of Prevention Services -- scaling up effective programs -- financing prevention services Stigma & Discrimination/ Social Support -- policies -- customs -- norms -- institutions Social Equity/Inequality -- race/ethnicity -- sex/gender -- age -- immigration/citizenship -- class/income/wealth Social Stability/Instability -- war -- violence -- migration -- famine

26. Thank you for your attention!