Pre-exposure Prophylaxis (PrEP): Review of Available Data and Models of Implementation

1. Pre-exposure Prophylaxis (PrEP): Review of Available Data and Models of Implementation Mark Thrun, MD Associate Professor, Division of Infectious Diseases University of Colorado Denver Director, HIV/STD Prevention and Control Denver Public Health

2. Disclosures of Financial Relationships This speaker has no financial relationships with commercial entities to disclose. This speaker will not discuss any off-label use or investigational product during the program. This slide set has been peer-reviewed to ensure that there are no conflicts of interest represented in the presentation.

3. Objectives • Provide an overview of human studies utilizing systemic antiretrovirals (ARVs) as PrEP • Provide evidence of ARV agents used as microbicides as PrEP • Discuss barriers to the implementation of PrEP

4. “No one knows whether PrEP will work. Even if it does, it will need to be used in combination with current HIV prevention methods, including safer sex, use of male and female condoms, treatment of sexually transmitted infections, risk reduction counseling, clean needles, and male circumcision. PrEP will never be a silver bullet and will not replace any of these current strategies.” AIDS Vaccine Advocacy Coalition – 2008

5. “No one knows whether PrEP will work. Even if it does, it will need to be used in combination with current HIV prevention methods, including safer sex, use of male and female condoms, treatment of sexually transmitted infections, risk reduction counseling, clean needles, and male circumcision. PrEP will never be a silver bullet and will not replace any of these current strategies.” AIDS Vaccine Advocacy Coalition – 2008

6. Courtesy Robert Grant, 2011

8. PrEP for conditions transmitted via sex not new: Medical contraception • Patient with knowledge of impending risk • Seeks out provider recommendation and/or prescription • Opportunity for education • Pregnancy avoidance techniques • Side effects and risks of medication • Risks of pregnancy if non-compliant • Presentation of pregnancy if prophylaxis not efficacious

9. NHBS Survey of MSM re: PrEP • To assess knowledge and attitudes towards PrEP in the prevention of HIV among MSM. • Supplemental PrEP-specific questions were included in the 2008 National HIV Behavioral Surveillance (NHBS) cycle in Denver, CO • Analysis limited to participants who did not report being HIV-positive • Descriptive frequencies presented

10. NHBS Overview • On-going surveillance activities conducted nationally in rotating 12-month cycles in three populations at high risk for HIV • Men who have sex with men (MSM) • Injection drug users (IDU) • High risk heterosexuals (HET) • Standardized core questionnaire across sites and populations (+ optional local questions) • A minimum of 500 persons per metropolitan area interviewed during each cycle • Anonymous and voluntary

11. National HIV Behavioral Surveillance System CDC funded, 20+ participating sites 12 month cycles in 3 target populations MSM2 cycle - 2008 Venue-based sampling IDU2 cycle - 2009 Respondent-driven sampling HET2 cycle - 2010 Respondent-driven sampling • Formative Research • Key Informant Interviews (N = 10) • Focus Group Interviews (N = 30) • Venue Identification • Formative Research • Key Informant Interviews (N = 10) • Focus Group Interviews (N = 30) • Seed Identification • Formative Research • Key Informant Interviews (N = 10) • Focus Group Interviews (N = 30) • Seed Identification • Surveillance Activities • Anonymous survey (N = 500) • Voluntary and anonymous HIV testing • Surveillance Activities • Anonymous survey (N = 500) • Voluntary and anonymous HIV testing • Surveillance Activities • Anonymous survey (N = 500) • Voluntary and anonymous HIV testing

12. NHBS-MSM2 (2008) • Venue-based, time-space sampling • Eligibility criteria: - Male, at least 18 years of age -Lives in the participating MSA - Able to complete the interview in English or Spanish - Not previously participated in NHBS-MSM2 • Interviewer administered survey via handheld ipaq • HIV testing: - Rapid Oral OraQuick - Confirmatory Oral OraSure

13. Result of most recent HIV test

14. Race / Ethnicity * Asian, Pacific Islander, American Indian, and Alaskan Native

15. Education

16. Age

17. PrEP Question Introduction Scientists are currently doing studies to find new ways of preventing people from becoming infected with HIV. In these studies, people take a pill every day that contains the same medicine that is used to treat people who are infected with HIV. Scientists want to know if taking this medicine will prevent people exposed to HIV from becoming infected with it. They call this method pre-exposure prophylaxis or PrEP.

18. Ever heard of PrEP before today?

19. Few or no side effects If studies showed that PrEP has few or no side effects, would you be willing to take PrEP pills every day to try to protect yourself from becoming infected with HIV?

20. 75% effective If studies showed that PrEP prevents HIV infection in three quarters or 75% of the people who take it, would you be willing to take PrEP pills every day to try to protect yourself from becoming infected with HIV?

21. 50% effective If studies showed that PrEP prevents HIV infection in half or 50% of the people who take it, would you be willing to take PrEP pills every day to try to protect yourself from becoming infected with HIV?

22. Low risk for infection Please tell me if the following are reasons why you might not consider taking PrEP: Because you think you are at low risk for HIV infection.

23. Consistent condom use Please tell me if the following are reasons why you might not consider taking PrEP: Because you use condoms consistently

24. Condom use and PrEP If you were taking PrEP pills every day, would you use condoms less frequently, more frequently, or about as frequently as before?

25. Sexual activity and PrEP If you were taking PrEP pills every day, would you have sex with fewer people, more people, or about the same number of people?

26. How effective is oral pre-exposure prophylaxis at prevention HIV? • 39% • 44% • 63% • 73% • 91% • 100%

27. iPrEx • Males, > 18 years • Normal renal and liver function • Sexual risk in the last 6 months • Unprotected anal intercourse with male partner with HIV or HIV unknown male partner • Anal sex with more than 3 males • Exchange sex • New STI • Randomized to placebo or tenofovir/emtricitabineevery day

28. In addition to medication • Monthly counseling • Risk behavior • Adherence • Monthly HIV testing • Frequent STD screening

29. Baseline demographics NEJM, Nov 23, 2010: Courtesy Robert Grant, 2011

30. 44% reduction in incident HIV in treatment versus placebo arm NEJM, Nov 23, 2010: Courtesy Robert Grant, 2011

31. Self-reported adherence associated with efficacy NEJM, Nov 23, 2010: Courtesy Robert Grant, 2011

32. Detectable drug associated with protection NEJM, Nov 23, 2010: Courtesy Robert Grant, 2011

33. PrEP very efficacious….if you can take it NEJM, Nov 23, 2010: Courtesy Robert Grant, 2011

34. Effective across subgroups NEJM, Nov 23, 2010: Courtesy Robert Grant, 2011

35. Nausea noted in some in 1st month NEJM, Nov 23, 2010: Courtesy Robert Grant, 2011

36. Few side effects NEJM, Nov 23, 2010: Courtesy Robert Grant, 2011

37. Resistance mutations NEJM, Nov 23, 2010: Courtesy Robert Grant, 2011

38. Vaginal PrEP could rescue HIV transmission by how much? • 39% • 44% • 63% • 73% • 91% • 100%

39. Microbicide Gel - Tenofovir • Caprisa 004 study – double-blind RCT • Tenovovir 1% gel vs. Placebo gel • Gel was used intra-vaginally, peri-coitally – within 12 hours before and 12 hours after sex • Adherence determined as proportion of sexual acts where a pre- and post-dose were administered • About 900 heterosexual women, South Africa Karim, Science, 2010

40. CDC TDF2 • HIV negative partners of HIV-infected persons randomized to TDF/FTC or placebo • 599 Placebo: 24 infections • 601 TDF/FTC: 9 infections • 62.6% reduction in risk • Sub-analysis of those with drug (<30 since last pickup) : 78% reduction in risk http://www.cdc.gov/nchhstp/newsroom/PrEPHeterosexuals.html

41. Kaplan-Meier time to HIV InfectionPlacebo 60 infections, Tenofovir 38 infections Karim, Science, 2010

42. UW Partners PrEP • 4,758 HIV-negative partners of HIV-infected persons randomized to: • Placebo: 47 infections • TDF: 18 infections – 62% reduction • TDF/FTC: 13 infections – 73% reduction

43. UW Partners PrEP Baeten, NELM, 2012

44. Fem-PrEP • Study of daily oral tenofovir/emtricitabine in women • Enrolled 1,951 women in Kenya, South Africa, Tanzania • Planned stop at 72 end points (HIV infection) • New HIV infections at 5% per year • Study discontinued at 56 endpoints • 28 HIV infections each in control and treatment arms • Unlikely to achieve statistical significance http://www.fhi360.org/en/Research/Projects/FEM-PrEP.htm

45. Reported condom use decreased in patients on PrEP (in iPrEx) by how much? • 5% • 10% • 25% • 50%

46. No behavioral disinhibition NEJM, Nov 23, 2010: Courtesy Robert Grant, 2011

47. Partners decreased NEJM, Nov 23, 2010

48. Condom use increased NEJM, Nov 23, 2010

49. More questions than answers

50. Who would be a high-risk person eligible for PrEP? • Risk category? • MSM • Heterosexuals • Injection drug users • Specific risk behaviors? • Multiple partners • Frequent unprotected anal or vaginal intercourse • Race/ethnicity?