1. Preparing for pre-exposure prophylaxis (PrEP) to prevent HIV infection James Wilton Project Coordinator Biomedical Science of HIV Prevention jwilton@catie.ca

2. 22 2 HIV/AIDS in Canada Number of people living with HIV 57,000 in 2005 65,000 in 2008 2,200 to 4,200 infected in 2005 2,300 to 4,300 infected in 2008 MSM (44%) IDU (17%) Women (26%) Aboriginal (12.5%) Source: Public Health Agency of Canada

3. 3 3 Improving HIV prevention 1.Do better with the strategies that we already have 2.Develop new biomedical technologies to prevent HIV 3.Adopt a more comprehensive approach to HIV prevention

4. 44 Turning to antiretrovirals for prevention The use of antiretrovirals for prevention by… 1.HIV-positive individuals to reduce their risk of transmitting HIV –Treatment as prevention 2.HIV-negative individuals to reduce their risk of infection –Post-exposure prophylaxis (PEP) –Pre-exposure prophylaxis (PrEP)

5. 5 What is pre-exposure prophylaxis (PrEP)? Pre  Before (and after) Exposure  When a fluid containing HIV comes into contact with mucous membranes or non-intact skin Prophylaxis  An action taken to prevent infection or disease

6. 66 What is PrEP to prevent HIV infection? The ongoing use of one or two antiretrovirals by HIV- negative individuals starting before an exposure and continuing afterwards A potential option to prevent infection from ongoing exposures to HIV during periods of risk A recently proven strategy still being studied PrEP is currently unapproved by Health Canada

7. 777 How does PrEP work? Infection does not occur instantly after an exposure to HIV The virus needs to spread throughout the body This may take up to 3 days after the exposure The “window of opportunity” for PrEP The brief period of time - after an exposure - where HIV has not yet spread throughout the body During this time, PrEP may be able to stop HIV from causing an infection

8. 8 Potential types of PrEP How are the antiretrovirals used? Oral pill Topical gel (microbicide) Rectal Vaginal Injection Intravaginal ring How often are the antiretrovirals used? Daily Intermittently Coitally (before/sex) How many antiretrovirals are used? Single Combination What antiretrovirals are used? Over 25 available

9. 9 What concerns does the use of PrEP raise? Side-effects and toxicity Drug resistance Adherence Risk compensation Access Cost

10. 10 What’s being researched? Large studies Viread or Truvada pill taken daily Viread  tenofovir Truvada  tenofovir + emtricitabine Tenofovir vaginal gel used before/after sex or daily Small Studies Gels used rectally Pills used intermittently or before/after sex Slow-release intravaginal rings Long-lasting injections Antiretrovirals other than tenofovir and emtricitabine

11. 11 How is the research conducted? Biomedical prevention trials Enrollment criteria Randomized Placebo-controlled Blinded

12. 12 How is the research conducted? Biomedical prevention trials Enrollment criteria Randomized Placebo-controlled Blinded Comprehensive package of prevention services Risk-reduction counseling Access to male and female condoms Adherence counseling HIV testing STI diagnosis and treatment

13. 13 How is the research conducted? Biomedical prevention trials Enrollment criteria Randomized Placebo-controlled Blinded Comprehensive package of prevention services Several outcomes measured HIV infections Adherence Side-effects and toxicity Risk behavior

14. 14 Limitations of biomedical prevention trials Ethical issues Measuring adherence Generalizability to other populations Applicability to the “real world”

15. 15 What does the research say about PrEP? Study participants PrEP strategy Reduced risk of HIV infection Overall Consistent users Safety concerns

16. 16 What does the research say about PrEP? CAPRISA 004 Study participantsHeterosexual women Type of PrEPCoital tenofovir gel (vaginal) Reduced risk of HIV infection Overall 39% Consistent users 54% Safety concerns Diarrhea

17. 17 What does the research say about PrEP? CAPRISA 004iPrEx Study participantsHeterosexual womenMen who have sex with men (MSM) and trans women Type of PrEPCoital tenofovir gel (vaginal) Daily Truvada pill Reduced risk of HIV infection Overall 39%44% Consistent users 54%73% Safety concerns Diarrhea Nausea Headache Decrease in kidney function and bone density Drug resistance

18. 18 What does the research say about PrEP? CAPRISA 004iPrExFEM-PrEP Study participantsHeterosexual women Men who have sex with men (MSM) and trans women Heterosexual women Type of PrEPCoital tenofovir gel (vaginal) Daily Truvada pill Reduced risk of HIV infection Overall 39%44%0% Consistent users 54%73%- Safety concerns Diarrhea Nausea Headache Decrease in kidney function and bone density Drug resistance No major safety concerns

19. 19 What does the research say about PrEP? CAPRISA 004iPrExFEM-PrEPTDF2 Study participantsHeterosexual women Men who have sex with men (MSM) and trans women Heterosexual women Heterosexual men and women Type of PrEPCoital tenofovir gel (vaginal) Daily Truvada pill Reduced risk of HIV infection Overall 39%44%0%63% Consistent users 54%73%-78% Safety concerns Diarrhea Nausea Headache Decrease in kidney function and bone density Drug resistance No major safety concerns Nausea Vomiting Dizziness

20. 20 What does the research say about PrEP? CAPRISA 004iPrExFEM-PrEPTDF2Partners PrEP Heterosexual women Men who have sex with men (MSM) and trans women Heterosexual women Heterosexual men and women Serodiscordant heterosexual couples Coital tenofovir gel (vaginal) Daily Truvada pill Daily Viread pill Daily Truvada pill 39%44%0%63%62% (Viread) 73% (Truvada) 54%73%-78%- Diarrhea Nausea Headache Decrease in kidney function and bone density Drug resistance No major safety concerns Nausea Vomiting Dizziness Nausea Diarrhea

21. 21 What do we know about PrEP? In combination with a comprehensive package of prevention services… 1.Daily Truvada reduced the risk of infection when used by MSM and trans women Heterosexual men and women 2.Daily Viread reduced the risk of infection when used by heterosexual men and women 3.A vaginal tenofovir gel used before and after sex reduced the risk of infection when used by women. It needs to be used consistently for it to work. The risk of side effects, toxicity, and drug resistance are low.

22. 22 What don’t we know about PrEP? Safety/effectiveness of… A pill taken occasionally A gel used in the rectum Long-lasting options (intravaginal ring or injection) Other antiretrovirals Safety/effectiveness of Viread, Truvada and tenofovir gel… In populations not included in trials Over a longer period of time In the “real world”

23. 23 What’s next for oral and topical PrEP? 1.Ongoing research

24. 24 Ongoing PrEP research StudyLocationPopulationInterventionCompletion CDC 4370Thailand2,400 people who use injection drugs Daily Viread pill2012 VOICEEast/South Africa 5,000 heterosexual women Daily Viread pill Daily Truvada pill Daily tenofovir gel 2013 Go to www.avac.org for latest trial informationwww.avac.org

25. 25 What’s next for oral and topical PrEP? 1.Ongoing research 2.Regulatory Approval Health Canada Safety and effectiveness data Off-label prescriptions

26. 26 What’s next for oral and topical PrEP? 1.Ongoing research 2.Regulatory Approval 3.Roll out Impact outside of a clinical trial

27. 27 Impact outside of a clinical trial 1.Uptake How many people are using it? Awareness – Do people know its available? Acceptability – Do people want to use it? Access – Can people access it if they want to? Who is using it? 2.Adherence Are people using it consistently and correctly? 3.Risk behavior Are people increasing their risk behavior?

28. 28 What’s next for oral and topical PrEP? 1.Ongoing research 2.Regulatory Approval 3.Roll out Impact outside of a clinical trial Comprehensive approach

29. 29 Integrating PrEP into a comprehensive approach Clinical services Non-clinical services

30. 30 Integrating PrEP into a comprehensive approach Clinical services Eligibility assessment and prescription HIV testing Drug resistance testing Medical and clinical monitoring STI treatment and diagnosis Non-clinical services

31. 31 Integrating PrEP into a comprehensive approach Clinical services Eligibility assessment and prescription HIV testing Drug resistance testing Medical and clinical monitoring STI treatment and diagnosis Non-clinical services Outreach and education Risk-reduction counseling Adherence support Advocacy

32. 32 What’s next for oral and topical PrEP? 1.Ongoing research 2.Regulatory Approval 3.Roll out Impact outside of a clinical trial Comprehensive approach Feasibility Open-label studies Demonstration projects

33. 33 CDC PrEP Guidelines In 2011, the CDC released interim guidance for healthcare providers on the prescription of PrEP “PrEP has the potential to contribute to effective and safe HIV prevention for MSM if 1.Targeted to MSM at high risk for infection 2.Delivered as part of a comprehensive set of prevention services (risk-reduction and adherence counseling, condom access, diagnosis and treatment of STIs) 3.Accompanied by monitoring of HIV status, side-effects, adherence, and risk behaviors at regular intervals”

34. 34

35. 35 CDC PrEP Guidelines Why were these guidelines released before regulatory approval? “Concerns exist that without early guidance, various unsafe and potentially less effective PrEP-related practises could develop” Such as… Use of other antiretrovirals Use of other dosing schedules Not screening for HIV status before initiating PrEP Providing in absence of other HIV prevention services

36. 36 Does PrEP have a role to play in Canada?

37. 37

38. 38

39. 39 CATIE Resources

40. 40 Thank you!