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?
HPTN 067, also known as the ADAPT Study, was designed to assess whether non-daily use of oral FTC/TDF as pre-exposure prophylaxis (PrEP), compared with daily use, would demonstrate equivalent coverage of sex acts, lower number of pills needed for coverage and decreased self-reported drug side effects over 24 weeks. The study also evaluated self-reported adherence and analyzed drug levels in the blood of participants.
Who participated in the study?
The study of more than 500 participants included women in Cape Town, South Africa, and men who have sex with men (MSM) and transgender women (TGW) in Bangkok, Thailand, and Harlem, N.Y.
What happened during the study?
After a four-week period of once-a-week directly observed dosing, participants were randomly assigned to one of three PrEP dosing regimens for 24 weeks: a) daily, b) time-driven: twice weekly with a post-sex dose, or c) event-driven: before and after sex. Study participants were given a Wisepill device that tracks each time a participant opens the container to take a pill. These data were then used by a study team member to conduct weekly phone or in-person interviews to ask participants if the date and time recorded by the Wisepill device did indeed involve taking a dose. Dates and times of sex events over the past week were also collected in these interviews. The interviews were for data collection only, so interviewers remained neutral and no messaging on adherence or non-adherence was provided, nor were data shared with study adherence counselors.
Blood samples were collected and analyzed for tenofovir (FTC/TDF) and their active metabolites at 10 and 30 weeks on study. In addition to overall adherence, the study evaluated PrEP coverage for each sex event, defined as taking at least one pill in the four days (96 hours) before the sex event and at least one pill within 24 hours after sexual intercourse. The regimens used in this trial and the definition of PrEP coverage was based on information that was available when the trial was designed in 2010. More current information suggests that higher concentrations of PrEP medications are required for protection from vaginal exposure to HIV, as would be afforded by daily oral dosing or any topical dosing.
Results:
Results from each group of participants were analyzed separately.
Thai MSM in Bangkok had the highest levels of coverage and adherence to the daily and time-driven dosing regimens. These were both significantly higher compared to the event-driven arm (85% of all sex events were covered in the daily arm, 84% in the time-driven arm and 74% in the event-driven arm). These findings indicate that some MSM and TGW could adhere to these non-daily PrEP regimens, though coverage was significantly lower in the event-driven arm.
In a cohort of young, predominantly Black MSM in Harlem, N.Y., participants had a statistically significant higher level of coverage of sex acts in the daily arm (66% of all sex events were completely covered) compared to the non-daily arms (47% of all sex events were covered in the time-driven arm; 52% of all sex events were covered in the event-driven arm). Adherence was significantly higher among those assigned to the daily arm compared to those assigned to the non-daily arms.
HPTN 067 demonstrated that young, single, black women in South Africa can take and adhere to a daily regimen of PrEP. This study showed high levels of coverage of sex acts in the daily arm (75%) among study participants in Cape Town when they were aware that the product works and that they were receiving the active product (i.e., in the setting of an open label study, not a placebo-controlled trial).
Study Documents
HPTN 067 Version 5.0
HPTN 067 Version 4.0
HPTN 067 Version 3.0
HPTN 067 Version 2.0
HPTN 067 Version 1.0
Presentations
- CROI 2016: HPTN 067/ADAPT Study: Predictors of coverage of sex events in PrEP regimens, Thai MSM-TGW
- CROI 2016: Modeled Effectiveness of Non-Daily PrEPBased on Sex Coverage Data from HPTN 067/ADAPT Study
- CROI 2016: Factors Associated with PrEP Coverage among MSM and TGW in NYCHPTN 067/ADAPT Study
- CROI 2015: HPTN 067/ADAPT Cape Town: A comparison of daily and nondaily PrEP dosing in African women
- CROI 2015: HPTN 067 Cape Town Results
Study Details
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.
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.
HIV-uninfected MSM/TGW, WSM at high risk of acquiring HIV infection.
540 evaluable participants, including 360 MSM/TGW and 180 WSM
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.
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.
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.
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.