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

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

~ 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

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

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

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

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

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

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

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

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

Illustrations Vaccine MCT ART 012, , 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

~ 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

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

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