1. Dr. Carol Odula (Obs./Gyn.) May 7 th 2013 Preparing for pre-exposure prophylaxis (PrEP) to prevent HIV infection

2. 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)

3. 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

4. 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

5. 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

6. 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

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

8. 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

9. 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 Several outcomes measured HIV infections Adherence Side-effects and toxicity Risk behavior

10. 10 What does the research say about PrEP? CAPRISA 004iPrExFEM-PrEPTDF2Partners PrEP Study participants Heterosexual women Men who have sex with men & transgender women Heterosexual women Heterosexual men and women Serodiscordant heterosexual couples Type of PrEPCoital tenofovir gel (vaginal) Daily Truvada pill Daily Viread pill Daily Truvada pill Reduced risk of HIV infection 39%44%0%63%62%(Viread)7 3% (Truvada) Consistent users 54%73%-78%- Safety concerns Diarrhea Nausea Headache Decrease in kidney fn and bone density Drug resistance No major safety concerns Nausea Vomiting Dizziness Nausea Diarrhea 10

11. 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?

12. What we do 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.

13. 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”

15. There is no magic pill