1. VIDI SYMPOSIUM Criteria Influencing Potential Impact of HIV Prevention Interventions January 14, 2008 Thomas Fleming, PhD University of Washington Fred Hutchinson Cancer Center

2. 1.Percent of HIV transmission risk being addressed ~ Size of the risk group: fraction of the incidence ~ Attributable risk of transmission pathway addressed ~ Potential for reduction in secondary transmission 2.Intervention: Plausible Reduction in Relative Risk ~ Strength of “proof of concept” data ~ Likelihood for effect on secondary transmission 3. Feasible level of coverage of the target population ~ Affordability, Acceptability, Practicality Criteria Influencing Potential Impact of HIV Prevention Interventions

4. ~ 27% : Black/Hispanic MSM ~ 16% : Black/Hispanic Non-MSM → 7% heterosexual ; 9% IDU ~ 24% : White MSM ~ 3% : White Non-MSM Men → 1% heterosexual ; 2% IDU ~ 19% : Black/Hispanic Women (Heterosexual) ~ 5% : Black/Hispanic Women (Non-Heterosex) → IDU ~ 4% : White Women (Heterosexual) ~ 2% : White Women (Non-Heterosexual) Size of the Risk Groups Fraction of the US Incidence

5. 1.Percent of HIV transmission risk being addressed ~ Size of the risk group: fraction of the incidence ~ Attributable risk of transmission pathway addressed ~ Potential for reduction in secondary transmission 2.Intervention: Plausible Reduction in Relative Risk ~ Strength of “proof of concept” data ~ Likelihood for effect on secondary transmission 3. Feasible level of coverage of the target population ~ Affordability, Acceptability, Practicality Criteria Influencing Potential Impact of HIV Prevention Interventions

6. Hypothetical Example ↓ in Substance Use in MSM 1. % of Tx risk addressed 11.25K (25% US incidence) ~ Size of risk group ~ 22.5K MSM ~ Attributable risk ~ 50% of MSM Tx ~ ↓ in secondary tx ( + ) 2.Plausible ↓ in RR 4.5K (10% US incidence) ~ Established POC? ~ Expect 40% ↓ in risk ~ ↓ in secondary tx ( ─ ) 3. Feasible coverage 2.25K (5% US Incidence) ~ Practical, Affordable? ~ Expect 50% coverage Criteria Influencing Potential Impact of HIV Prevention Interventions

7. 1.Percent of HIV transmission risk being addressed ~ Size of the risk group: fraction of the incidence ~ Attributable risk of transmission pathway addressed ~ Potential for reduction in secondary transmission 2.Intervention: Plausible Reduction in Relative Risk ~ Strength of “proof of concept” data ~ Likelihood for effect on secondary transmission 3. Feasible level of coverage of the target population ~ Affordability, Acceptability, Practicality Criteria Influencing Potential Impact of HIV Prevention Interventions

8. Hypothetical Example ↓ in Substance Use in MSM 1. % of Tx risk addressed 11.25K (25% US incidence) ~ Size of risk group ~ 22.5K MSM ~ Attributable risk ~ 50% of MSM Tx ~ ↓ in secondary tx ( + ) 2.Plausible ↓ in RR 4.5K (10% US incidence) ~ Established POC? ~ Expect 40% ↓ in risk ~ ↓ in secondary tx ( ─ ) 3. Feasible coverage 2.25K (5% US Incidence) ~ Practical, Affordable? ~ Expect 50% coverage Criteria Influencing Potential Impact of HIV Prevention Interventions

9. 1.Percent of HIV transmission risk being addressed ~ Size of the risk group: fraction of the incidence ~ Attributable risk of transmission pathway addressed ~ Potential for reduction in secondary transmission 2.Intervention: Plausible Reduction in Relative Risk ~ Strength of “proof of concept” data ~ Likelihood for effect on secondary transmission 3. Feasible level of coverage of the target population ~ Affordability, Acceptability, Practicality Criteria Influencing Potential Impact of HIV Prevention Interventions

10. Hypothetical Example ↓ in Substance Use in MSM 1. % of Tx risk addressed 11.25K (25% US incidence) ~ Size of risk group ~ 22.5K MSM ~ Attributable risk ~ 50% of MSM Tx ~ ↓ in secondary tx ( + ) 2.Plausible ↓ in RR 4.5K (10% US incidence) ~ Established POC? ~ Expect 40% ↓ in risk ~ ↓ in secondary tx ( ─ ) 3. Feasible coverage 2.25K (5% US Incidence) ~ Practical, Affordable? ~ Expect 50% coverage Criteria Influencing Potential Impact of HIV Prevention Interventions

11. 1.Percent of HIV transmission risk being addressed ~ Size of the risk group: fraction of the incidence ~ Attributable risk of transmission pathway addressed ~ Potential for reduction in secondary transmission 2.Intervention: Plausible Reduction in Relative Risk ~ Strength of “proof of concept” data ~ Likelihood for effect on secondary transmission 3. Feasible level of coverage of the target population ~ Affordability, Acceptability, Practicality Criteria Influencing Potential Impact of HIV Prevention Interventions

12. Hypothetical Example ↓ in Substance Use in MSM 1. % of Tx risk addressed 11.25K (25% US incidence) ~ Size of risk group ~ 22.5K MSM ~ Attributable risk ~ 50% of MSM Tx ~ ↓ in secondary tx ( + ) 2.Plausible ↓ in RR 4.5K (10% US incidence) ~ Established POC? ~ Expect 40% ↓ in risk ~ ↓ in secondary tx ( ─ ) 3. Feasible coverage 2.25K (5% US Incidence) ~ Practical, Affordable? ~ Expect 50% coverage Criteria Influencing Potential Impact of HIV Prevention Interventions

13. Illustrations Vaccine MCT ART 012, 046 052, 060, Voice 1. % of Tx risk addressed ~ Size of risk group ++ + + ~ Attributable risk ++ ++ ++ ~ ↓ in secondary tx (+/─) ( ─ ) (+/─) 2.Efficacy of intervention ~ Established POC? ? ++ ? ~ ↓ in secondary tx ( ? ) ( ─ ) ( ? ) 3. Feasible coverage ~ Practical, Affordable? + +/─ + Criteria Influencing Potential Impact of HIV Prevention Interventions

14. ~ 27% : Black/Hispanic MSM ~ 16% : Black/Hispanic Non-MSM → 7% heterosexual ; 9% IDU ~ 24% : White MSM ~ 3% : White Non-MSM Men → 1% heterosexual ; 2% IDU ~ 19% : Black/Hispanic Women: Heterosexual ~ 5% : Black/Hispanic Women: IDU ~ 4% : White Women: Heterosexual ~ 2% : White Women: IDU Size of the Risk Groups Fraction of the US Incidence

15. 1.Percent of HIV transmission risk being addressed ~ Size of the risk group: fraction of the incidence ~ Attributable risk of transmission pathway addressed ~ Potential for reduction in secondary transmission 2.Intervention: Plausible Reduction in Relative Risk ~ Strength of “proof of concept” data ~ Likelihood for effect on secondary transmission 3. Feasible level of coverage of the target population ~ Affordability, Acceptability, Practicality Criteria Influencing Potential Impact of HIV Prevention Interventions

16. VIDI SYMPOSIUM The Way Forward for HIV Prevention: Combination Strategies (HAARP) Domestic & International Vaccines Microbicides ART MCT STD IDU Behavioral