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

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

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

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 tenofovir gel used daily Rectal tenofovir gel used before and after sex Truvada tablets taken daily  Each participant will follow all of 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

MTN-017 study design Product Sequence Period 1 (8 weeks) Product Break (1 week) Period 2 (8 weeks) Product Break (1 week) Period 3 (8 weeks) 1Daily Truvada Daily rectal gel Rectal gel before and after sex 2 Daily Truvada Daily rectal gel 3 Rectal gel before and after sex Daily Truvada 4Daily rectal gel Daily Truvada Rectal gel before and after sex 5Daily Truvada tablets Rectal gel before and after sex Daily rectal gel 6Rectal gel before and after sex Daily Rectal gel Daily Truvada

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

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? Primary objectives: Safety and Acceptability

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

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

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

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

Rectal microbicides timeline Phase I (MTN-006/ MTN-007) Phase II (MTN-017) Phase IIb Review Available

What’s next in our timeline? Finalize MTN-017 draft protocol MTN-017 PSRC review on April 3rd March/April 2012 MTN-017 underway! Mid 2012

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

Thank You!