HPTN 067
The ADAPT Study
A Phase II, Randomized, Open-Label, Pharmacokinetic and Behavioral Study of the Use of Intermittent Oral Emtricitabine/Tenofovir Disoproxil Fumarate Pre-Exposure Prophylaxis (PrEP)
What is HPTN 067?
Protocol Status: Enrolling
Study Purpose: This is a behavioral study to evaluate the feasibility of intermittent dosing of a pre-exposure prophylaxis (PrEP) regimen. Recommendations for intermittent usage, compared with daily usage, may provide comparable coverage of possible exposures with pre- and post-exposure dosing, decreased pill requirements, and decreased symptoms. This study is designed to optimize and facilitate future efficacy research, to be proposed separately. The study aims to identify dosing regimens that foster healthy sexual practices and pill-taking behavior in people at high risk of human immunodeficiency virus (HIV) infection. The word ADAPT in the study title is an acronym for Alternative Dosing to Augment PrEP pill-Taking.
Study Design: A Phase II randomized open-label clinical trial of oral Truvada® [tenofovir disoproxil fumarate (TDF) plus emtricitabine (FTC)] PrEP among HIV-uninfected men who have sex with men and transgender women (MSM/TGW) and women who have sex with men (WSM), at high risk of acquiring HIV infection. The study includes a six week lead-in period which includes directly observed therapy (DOT) at Enrollment and Weeks 1 through 4, followed by one week without dosing to determine individual steady state pharmacokinetics (PK). This will provide the opportunity to create a pharmacokinetic analysis of drug levels to be expected at given rates of intake (adherence). Participants will then be randomly assigned to one of three dosage groups in a 1:1:1 ratio: daily dosing, time-driven dosing, and event-driven dosing. After randomization, participants will then complete a 24-week period of self-administered dosing (Weeks 6 through 30), with one visit four weeks after the completion of dosing (34 weeks total). Participants who acquire HIV infection during the study discontinue dosing and will be followed until study closure and referred for post-trial care as per local regulations. A subset of participants in each of the study arms will also participate in a qualitative evaluation of the social and behavioral aspects of differing dosing strategies utilizing focus groups after Week 34. A subset of clinic staff who directly interact with participants regarding pill-taking and sexual risk behavior, as well as a subset of participants identified as particularly informative will participate in key-informant interviews after Week 34.
Study Population: HIV-uninfected MSM/TGW, WSM at high risk of acquiring HIV infection.
Study Size: 540 evaluable participants, including 360 MSM/TGW and 180 WSM
Study Duration: The total duration of the study will be less than two years. Enrollment is planned over 8 months. Follow-up will include a 30-week dosing period, with a single (final) visit four weeks after completion of dosing. The 30-week dosing period includes a 6-week lead-in period which includes once-a-week DOT administered at Enrollment and Weeks 1 through 4, followed by one week without dosing. The lead-in phase will be followed by 24 weeks of self-administered use, a 4 week off-drug period, and a final clinic visit at Week 34.
Treatment Regimen: Oral FTC/TDF in three dosage groups: daily dosing, time-driven dosing, and event-driven dosing. The time-driven dosing group will be asked to take FTC/TDF twice weekly with a post-exposure boost. The event-driven dosing group will be asked to take FTC/TDF before and after a potential exposure to HIV infection. In all three dosing groups, dosing will not exceed two doses per day or seven doses per week.
Primary Objectives: To test the hypothesis that recommending intermittent (non-daily) usage of oral FTC/TDF chemoprophylaxis, compared with recommending daily usage, will be associated with: 1) Equivalent coverage of sex events with pre- and post-exposure dosing; 2) Lower number of pills needed for coverage and fewer pills used; and 3) Decreased self-reported symptoms/side effects (both severity and frequency) during 24 weeks of self-administered use.
Secondary Objectives: 1) Develop objective measures of drug exposure by obtaining steady state pre-dose “trough” drug concentration in several biological matrices for participants during a lead-in period of weekly DOT; 2) To describe safety outcomes among PrEP users including adverse events among all participants and drug resistance and plasma HIV ribonucleic acid (RNA) levels among participants who seroconvert; 3) Assess differences between arms in the acceptability of different PrEP regimens and in perceptions of advantages and disadvantages of different regimens; 4) Assess differences by arm in adherence; and 5) Evaluate the potential influence of PrEP usage on changes in sexual behavior, planning for sex, prediction of risky situations, and recognition of possible HIV exposure from baseline to final on-drug assessment in relation to PrEP optimism.
Protocol Team Member: Albert Liu get info
Protocol Team Member: Ana Martinez get info
Protocol Team Member: Craig Hendrix get info
Protocol Team Member: David Galetta get info
Protocol Team Member: Estelle Piwowar-Manning get info
Protocol Team Member: James Dai get info
Protocol Team Member: James Hughes get info
Protocol Team Member: James Rooney get info
Protocol Team Member: Janet McNicholl get info
Protocol Team Member: John Gagnon get info
Protocol Team Member: Laura McKinstry get info
Protocol Team Member: Linda-Gail Bekker get info
Protocol Team Member: Michael Hendry get info
Protocol Team Member: Michael Stirratt get info
Protocol Team Member: Prempreeda Pramoj Na Ayutthaya get info
Protocol Team Member: Rhonda White get info
Protocol Team Member: Rivet Amico get info
Protocol Team Member: Robert Klitzman get info
Protocol Team Member: Surita Roux get info
Protocol Team Member: Susan Eshleman get info
Protocol Team Member: Tim Mastro get info
Protocol Team Member: Vanessa Elharrar get info
Protocol Co-Chair: Frits van Griensven get info
Protocol Co-Chair: Nirupama Sista get info
Protocol Co-Chair: Robert Grant get info
CORE Protocol Specialist: Bonnie Dye get info
CORE Protocol Specialist: Kevin Bokoch get info
CORE Protocol Specialist: Scott Rose get info
| Site |
Target Enrollment |
Cumulative Enrollment |
Implementation Status |
More Info |
|---|---|---|---|---|
|
30346 Cape Town, South Africa |
191 |
191 |
Enrollment Closed |
get more |
|
31681 Bangkok, Thailand |
180 |
129 |
Enrolling |
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|
Harlem Prevention Ctr. CRS (El-Sadr CTU) 30276 New York, United States |
180 |
53 |
Enrolling |
get more |
