Looking Ahead to MTN-017

1. Looking Ahead to MTN-017 Ross D. Cranston MD, FRCP Microbicide Trials Network IRMA

2. Rationale: Key points • Unprotected receptive anal intercourse is a high risk sexual activity for HIV transmission • We need products to prevent HIV through anal sex – commonly practiced by both men and women around the world • Animal studies and an early clinical study have shown vaginal tenofovir gel has an anti-HIV effect when used in the rectum • More information about the safety and acceptability of tenofovir gel as a rectal microbicide is necessary to move forward

3. MTN-017 protocol overview • Design and rationale • Study objectives • Participants and enrollment • Study procedures • Safety monitoring • Timelines • Questions and discussion

4. How MTN-017 is designed • Phase II trial evaluating safety and acceptability • Will include 186 men who have sex with men and transgender women • Study regimens will include: • Rectal tenofovirgel used daily • Rectal tenofovirgel used before and after sex • Truvadatablets taken daily • Each participant will follow allof the study regimens for eight weeks, with a weeklong break between regimens when no product will be used • The order in which participants follow study regimens will be based on random assignment • All participants will receive standard HIV prevention package

5. MTN-017 study design

6. About the study products • Rectal-friendly formulation of tenofovir gel • Tenofovir gel for vaginal use modified to have less glycerin • Rectal-friendly formulation evaluated in MTN-007 • Truvada tablets • Brand name for combination drug containing tenofovir and emtricitabine • iPrEX study showed Truvada reduced the risk of HIV infection among men who have sex with men by nearly 44 percent when used daily compared a placebo tablet

7. Primary objectives: Safety and Acceptability • Compare the safety profiles of rectal tenofovir gel used daily and before and after sex, and Truvada tablets • Evaluate and compare the acceptability of Truvada tablets to rectal tenofovir gel, i.e., did they like the product?; would they use it in the future, if available?

8. Secondary objectives • Estimate adherence to the products, i.e. did they use the product? (Examples: SMS, Computer Assisted Self Interview, applicator/pill count) • Measure drug levels (blood and tissues) • Examine whether sexual activity or condom use varies by product • Determine the level of product sharing with non-participants • Determine practices associated with anal sex that could detract from microbicide effectiveness, i.e. lubes, douching

9. Who can participate? • HIV-uninfected, men who have sex with men and transgender women 18 and older who have practiced receptive anal intercourse within the last three months • Participants must also meet other inclusion and exclusion criteria to ensure they are in general good health

10. Study visits and procedures • Screening visit • Informed consent • Physical and rectal exams • HIV risk reduction counseling • Enrollment visit • Randomization of participants • Follow-up visits • Monthly • Visit procedures • Physical exams • Rectal exams • Urine and blood tests • Rectal biopsies (flexible sigmoidoscopy) at some sites • Behavioral surveys

11. MTN-017: Summary First Phase II trial of a rectal microbicide for HIV prevention through receptive anal sex Seeks to answer whether tenofovir gel is safe and acceptable as a rectal microbicide Will involve 186 men who have sex with men and transgender women at trial sites in South Africa, Peru, Thailand and the United States Designed to provide the safety data sufficient to move forward with a large effectiveness study Anticipated to begin mid 2012; results late 2013

12. Rectal microbicides timeline

13. What’s next in our timeline?

14. Acknowledgements MTN is funded by NIAID (5U01AI068633), NICHD and NIMH, all of the U.S. National Institutes of Health

15. Thank You!