1. Pre-exposure Prophylaxis (PrEP) for HIV Prevention: What’s the Future? Joanne Stekler, MD MPH Assistant Professor of Medicine University of Washington Regional Strategy Symposium and Workshops on HIV Prevention and Treatment in MSM May 10, 2013

2. Outline PrEP: Pre-Exposure Prophylaxis 1)Effectiveness of PrEP 2)The importance of being adherent … and other concerns 3)What are we doing about PrEP in Seattle?

3. Can a pill prevent HIV?

4. Three trials have demonstrated PrEP efficacy in MSM and heterosexual men and women Study, population PrEP agent # of HIV infections PrEP efficacy PrEPplacebo iPrEx MSM n=2499 Brazil, Ecuador, Peru, South Africa, Thailand, US FTC/TDF3664 44% Grant NEJM 2010 Partners PrEP Study Heterosexual couples n=4758 Kenya, Uganda TDF17 52 67% FTC/TDF13 75% Baeten NEJM 2012 TDF2 Study Heterosexuals n=1219 Botswana FTC/TDF1026 62% Thigpen NEJM 2012

5. The importance of being adherent. And your other concerns.

6. Divergent PrEP trial results StudyPopulationNResults iPrExMSM249944% efficacy FTC/TDF Partners PrEP Study Heterosexual couples 4758 67% efficacy TDF 75% efficacy FTC/TDF TDF2 Study Men and women 121962% efficacy FTC/TDF FEM-PrEPWomen20216% efficacy FTC/TDF VOICEWomen 3021 (oral arms) No efficacy TDF No efficacy FTC/TDF Bangkok Tenofovir Study IDUs2400TDF ongoing

7. The importance of being adherent Baeten et al N Engl J Med 2012 Grant et al N Engl J Med 2010 Van Damme et al N Engl J Med 2012 Thigpen et al N Engl J Med 2012 Marrazzo et al CROI 2013 #26LB Efficacy in randomized comparison % of blood samples with tenofovir detected Partners PrEP75%81% TDF262%79% iPrEx44%51% FEM-PrEP6%26% VOICE-29%

9. What about sexual risk-taking? iPrEx Partners PrEP 50 30 10 0 0612182430 Follow-up time (Month) 40 20 3915212733 Proportion of HIV – participants with any unprotected sex (%) TDFFTC/TDFPlacebo In both iPrEx and Partners PrEP, unprotected sex was less common over time. BUT subjects did not know if they were on PrEP or placebo.

10. HIV seroconverters with antiretroviral drug resistance HIV infected after enrollment Acute HIV infection at enrollment # HIV infections averted iPrEx0 / 362 / 228 Partners PrEP0 / 302 / 874 TDF20 / 101 / 116 Resistance = K65R (TDF) or M184V/I (FTC) mutations What about drug resistance?

11. PrEP and HIV resistance Zone of Resistance Risk No Drug No Resistance Infection No Infection No Resistance Adherence / Drug Exposure HIV infection Resistant infection Risk of resistance (red) HIV protection (blue) LowHigh Slide modified from John Mellors, FDA 2012

12. FDA approves Truvada as PrEP: July 2012 Deborah Birnkrant, director of the Division of Antiviral Products, FDA July 16, 2012

13. CDC provides interim guidance for use of PrEP in MSM and heterosexuals

14. What are we doing about PrEP in Seattle?

15. Novel Exploration of Therapeutics for PrEP uwactu uwactu.org help research research helps

16. Can we target to the highest risk populations? Will they be willing to take PrEP? Will they be adherent? How do we monitor PrEP? HIV testing Recognition of acute HIV infection Drug resistance Will they change sexual behavior because of PrEP?

17. Insured Primary care providers  Will insurance pay for it? Uninsured Public Health? Madison Clinic? Community health clinic? Other?

18. Preparing for PrEP in Seattle Study Schema Purpose: Assess uptake/demand for PrEP among high risk persons in Seattle Describe uptake & patterns of use by insurance status Explore use of Wisepill as a novel technology for adherence support Design: open-label cohort study Population: High risk MSM Men and women reporting unprotected sex in discordant couples Study size: >50 subjects, followed for at least 6 months Partners: Gay City, Gilead, WA DOH, community pharmacies Timeline: anticipated start in July?

19. Preparing for PrEP in Seattle Inclusion criteria high risk HIV-negative 18 years old Exclusion criteria symptoms of acute HIV infection impaired kidney function active hepatitis B infection pregnant

20. Preparing for PrEP in Seattle Wisepill

21. Condoms Treatment Needle Exchange HIV Testing & Serosorting? PrEP Vaccines HIV and STI