Prevention Trials in the Region Behavioral Trials* Author (Year) Location Intervention Findings (Rate ratio (RR)) Ross (2007) Tanzania MEMA kwa Vijana, adolescent sexual health education in primary school, condoms, health services RR=0.75 (0.34, 1.66) (Girls only) Corbett (2007) Zimbabwe Workplace onsite VCT vs. standard VCT at external provider RR=1.49 (0.79, 2.80) Jewkes (2008) South Africa Stepping Stones, 50-hr participatory learning approach vs. 3-hr standard intervention on safer sex and HIV RR=0.95 (0.67, 1.35) Pequagnat (2008) Community popular opinion leader To be announced *Limited to interventions evaluated by randomized controlled designs with HIV incidence as an outcome

Prevention Trials in the Region Microcredit Trials* Author (Year) Location Intervention Findings (Risk ratio (RR)) Pronyk (2006) South Africa IMAGE Intervention, poverty-focused microfinance, 12-15 month Sisters for Life gender and HIV training program RR=1.06 (0.66, 1.69) *Limited to interventions evaluated by randomized controlled designs with HIV incidence as an outcome

Prevention Trials in the Region Male Circumcision Trials* Author (Year) Location Intervention Findings (Rate ratio (RR)) Auvert (2005) South Africa Male circumcision vs. delayed circumcision RR=0.40 (0.24-0.68) Bailey (2007) Kenya RR=0.47 (0.28, 0.78) (Risk Ratio) Gray (2007) Uganda RR=0.49 (0.28, 0.84) *Limited to interventions evaluated by randomized controlled designs with HIV incidence as an outcome

Male Circumcision Reduces FM transmission by ~ 58% Challenge for reduction in MF is ensuring sufficient time for wound healing before resumption of sexual activity Little evidence of risk compensation in RCTs: critical consideration for scale-up

Prevention Trials in the Region Microbicide Trials* Author (Year) Location Intervention Findings (Hazard ratio (HR)) Kreiss (1992) Kenya Nonoxynol-9 sponge vs. placebo HR=1.7 (0.9, 3.0) Richardson (2001) Nonoxynol-9 vaginal gel vs. placebo RR=0.7 (0.3, 1.5) (Risk Ratio) VanDamme (2002) South Africa HR=1.5 (1.0, 2.2) VanDamme (2008) South Africa, Uganda Cellulose sulfate vs. placebo HR=1.61 (0.86, 3.01) Skoler-Karpoff (2008) Carraguard vs. methylcellulose HR=0.87 (0.69, 1.09) *Limited to interventions evaluated by randomized controlled designs with HIV incidence as an outcome

Microbicide evolution: Non-specific  ARV-containing products Holds more promise Topical, vaginal PREP To prevent transmission (reduce infectiousness)? Shift from original concept of low-tech, low-cost product Challenges with resistance Use during pregnancy Not effective on other STI outcomes Not a contraceptive

Prevention Trials in the Region Cervical Barrier Trials* Author (Year) Location Intervention Findings (Hazard ratio (HR)) Padian (2007) South Africa, Zimbabwe Latex diaphragm, lubricant gel, and condoms vs. condoms alone HR=1.05 (0.84-1.32) *Limited to interventions evaluated by randomized controlled designs with HIV incidence as an outcome

Prevention Trials in the Region STI Treatment Trials* Author (Year) Location Intervention Findings (Rate ratio (RR)) Grosskurth (1995) Tanzania Improved STD case management at primary health care level 0.58 (0.42, 0.79) Wawer (1999) Uganda Intensive STD control, via home-based mass antibiotic treatment 0.97 (0.81, 1.16) Kaul (2004) Kenya Monthly administration of 1 g of azithromycin or identical placebo 1.2 (0.6, 2.5) Gregson (2007) Zimbabwe community-based peer education, condom distribution, income-generating projects, and clinic-based STI treatment and counseling 1.27 (0.92, 1.75) *Limited to interventions evaluated by randomized controlled designs with HIV incidence as an outcome

Prevention Trials in the Region STI Treatment Trials* (con’t) Author (Year) Location Intervention Findings (Rate ratio (RR)) Watson-Jones (2008) Tanzania HSV-2 suppressive treatment with 400mg vs. placebo 1.08 (0.64, 1.83) Kamali (2003) Uganda Behavioral interventions alone (A), behavioral and STI interventions (B), or routine government health services and community development activities (C) RR=0.94 (0.60, 1.45) Group A vs. C RR= 1.00 (0.63, 1.58) Group B vs. C *Limited to interventions evaluated by randomized controlled designs with HIV incidence as an outcome

Epidemic Phase: A Guide in Designing HIV Prevention Strategy Key Strategy Considerations HIV+ partners Rare Common Sub-pop’n distribution of HIV Concentrated in core groups Majority in stable partnerships Acute/early HIV inf’n (Incidence:Prevalence) Higher I:P ratio Lower I:P ratio Biological & behavioral susceptibility High Lower Behavior change at individual & societal levels (e.g. condoms, #sp, ART) Low Increasing STDs Bacterial GUD & other STDs common in core groups Bacterial GUD replaced by HSV-2; Other bacterial STDs falling HIV Epidemic Pattern Mature/Generalized Nascent  Concentrated EpidemicPhase Hyperendemic Growth Decline Endemic Modified from: Wasserheit & Aral. JID 1996;174:S201-213

Prevention Trials in the Region Vaccine Trials* Author (Year) Location Intervention Findings (Hazard ratio (HR)) HVTN 503 South Africa HVTN 503: Phambili MRKAd5 HIV-1 gag/pol/nef Enrolling *Limited to interventions evaluated by randomized controlled designs with HIV incidence as an outcome

What works? No HIV vaccine or topical prophylaxis will be available in the foreseeable future For now: male condoms (condom promotion, distribution & IES); VCT and peer-based programs; male circumcision; and the prophylactic use of ARVs to reduce MTCT or contraception to prevent unwanted pregnancy Treatment of sexually transmitted infections, a strong public health intervention in its own right, has had mixed results Might be more effective if focused on reducing infectiousness than acquisition

Levels of evidence for HIV prevention Abstinence Male circumcision Male condom Female condom Reducing # of sex partners (absolute and concurrent) STD tx for HIV Abstinence promotion, with or without Postponing sexual debut More evidence Less evidence

What we need to do: Combination prevention packages No single magic bullet + behavior: Essential to maintain adherence, to avoid sexual dis-inhibition (risk compensation) + structural: Essential for addressing mechanisms that are necessary for scale-up to optimize effects + biological: (e.g. male circumcision plus condoms; cervical barrier plus vaginal antimicrobial or antiretroviral gel)

Whom to target Universalistic Prioritization/targeting/tailoring Precision with or without diffusion Potential for greater yet limited impact Stigma Restricted benefits Restricted effects Dilution Equality Equal access Tipping point for social norms

Relevant issues UNAIDS guidelines for planning purposes useful first step Epidemics: low-level, concentrated, generalized or hyper-endemic Key steps: “know epidemic and current response” “match and prioritize response” “set ambitious, realistic and measurable prevention targets” “tailor prevention plans” “utilize and analyze strategic information” Guidelines may not accurately reflect real setting complexities, no specifics on how to choose optimal sets of interventions by situation, no focus on best-buys   Academic studies have serious limitations

Challenges for decision makers Finding the optimal balance between treatment, prevention, and palliative interventions Few good tools to choose sets of interventions that yield optimal results for specific settings (demographics, epidemic characteristics, economic context, etc.) and financing levels. Political and social considerations affect decision making: some cost-effective interventions hard to promote

Levels of outcomes/impact Environmental e.g. Changes in social and sexual norms Cognitive, attitudinal, affective e.g. fear of stigma Behavioral e.g. Condom use Biological HIV STI Pregnancy