A Phase II Randomized, Double-Blind, Study of the Safety and Tolerability of Maraviroc (MVC), Maraviroc + Emtricitabine (MVC+FTC), Maraviroc + Tenofovir disoproxil fumarate (MVC+TDF), or Tenofovir disoproxil fumarate + Emtricitabine (TDF+FTC) for Pre-Exposure Prophylaxis (PrEP) to Prevent HIV Transmission in At-Risk Men Who Have Sex with Men and in At-Risk Women
What is HPTN 069?
HPTN 069/ACTG 5305 was a study to learn more about the safety and acceptability of oral maraviroc in at risk HIV uninfected men who have sex with men (MSM) and in at-risk HIV uninfected women.
Who participated in the study?
406 MSM and 188 women were enrolled at 13 sites in the United States and Puerto Rico.
What happened during the study?
Study participants were randomly assigned to one of four arms: once-daily maraviroc alone, maraviroc plus TDF, maraviroc plus emtricitabine, or TDF and emtricitabine (FTC). The study participants and the study researchers were blinded to the study arm randomizations.
The study was an important next step in helping to determine if future research should be done to see if maraviroc-containing regimens can be used as PrEP. There are some concerns about the possibility of side effects and resistance related to the antiretrovirals (ARVs)that are currently used for PrEP. Resistance means that some strains of HIV can no longer be treated with certain ARVs. Maraviroc is an approved drug that blocks entry of HIV into cells, and is also not widely used for treatment. It has been shown to be safe for use by HIV-infectedpeople and rarely causes drug resistance.
The results for the men’s cohort found that the maraviroc-containing regimens were as safe and well-tolerated as TDF/FTC. Five participants became infected with HIV in the men’s cohort. These participants had low, variable or undetectable drug levels, likely indicating they were not consistently taking their pills
The researchers also reported results from a substudy evaluating the impact of these regimens on colorectal tissue samples from 55 participants. Previous work in HIV-infected people had suggested that maraviroc may increase immune T-cell activation in rectal tissue, which potentially could increase susceptibility to HIV infection. However, the researchers did not observe increased T-cell activation in the samples. Viral suppression experiments with tissue samples taken from study participants provided a preliminary indication that maraviroc alone may be less effective at preventing HIV infection than combination PrEP regimens.
The women’s cohort primary results were presented at AIDS 2016 in Durban, South Africa.
HPTN 069 Version 3.0
- HPTN 069 Version 3.0 (03 Jan 2013)
- LOA #5 (24 Feb 2015)
- LOA #4 (14 Jul 2014)
- LOA #3 (5 Mar 2014)
- LOA #2 (1 Jul 2013)
- LOA #1 (24 May 2013)
- V3 Clarification Memo #1 (13 Jan 2014)
HPTN 069 Version 2.0
- HPTN 069 Version 2.0 (09 Apr 2012)
- V2 Clarification Memo #4 (25 Sep 2012)
- V2 Clarification Memo #3 (24 Sep 2012)
- V2 Clarification Memo #2 (24 Aug 2012)
- V2 Clarification Memo #1 (26 Apr 2012)
More Study Documents
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To assess the safety and tolerability of four antiretroviral (ARV) drug regimens used as pre-exposure prophylaxis (PrEP) to prevent HIV transmission in a population of at-risk men who have sex with men (MSM) and in at-risk women.
Phase II, four-arm, multisite, randomized, double-blinded trial.
HIV-uninfected at-risk MSM and at-risk women recruited from sites in the United States (U.S.).
Sites are strongly encouraged to enroll young adult (aged 18-25) MSM and/or MSM or women of color to maximize representation from these groups. Each site will be asked to work with their Community Advisory Boards (CABs) and outreach, education and recruitment teams to develop a recruitment plan that will focus on the engagement of MSM who are younger and/or MSM and women of color.
Four hundred (400) MSM and 200 women. Seventy-two (72) participants (18 per arm) will be asked to enroll in a Drug Interaction Subset. Sixty (60) men and 60 women (15 male/15 female per arm) at selected sites will be asked to enroll in a Tissue Subset.
Approximately 30 months. Accrual will occur in a staggered fashion, with men beginning first, and women beginning several months later. Accrual for the men will require approximately 9 months, and accrual for the women will require approximately 9 months. Each participant will be followed for approximately 12 months (study drug will be stopped at Week 48, with a final post-study drug visit at Week 49).
The antiretroviral drugs (ARVs) being used in this study are: maraviroc (MVC) 300 mg, emtricitabine (FTC) 200 mg, tenofovir disoproxil fumarate (TDF) 300 mg, and matching placebos. Participants will be randomized to one of four arms as follows: Arm 1: MVC 300 mg + [FTC placebo] + [TDF placebo] orally once daily.
Arm 2: MVC 300 mg + FTC 200 mg + [TDF placebo] orally once daily.
Arm 3: MVC 300 mg + [FTC placebo] + TDF 300 mg orally once daily.
Arm 4: [MVC placebo] + FTC 200 mg + TDF 300 mg orally once daily.
Study Regimen = 3 pills daily; all arms receive at least one active drug.
To assess the safety and tolerability of MVC, MVC+FTC, MVC+TDF, and TDF+FTC over 48 weeks.
This will be measured by the occurrence of Grade 3 and higher adverse events (safety) and time to
permanent discontinuation (tolerability) in each of the four study arms.
1) Assess Grade 2 and higher adverse events, and Grade 1 clinical (non-laboratory) adverse events that lead to a temporary or permanent hold in study drug. 2) Assess changes in lipids in each of the four study arms. 3) Assess changes in bone mineral density in each of the four study arms. 4) Evaluate interactions of MVC, FTC, and TDF in the four study arms in a subset of participants (Drug Interaction Subset). 5) Evaluate concentrations of MVC, FTC, tenofovir (TFV) and their phosphorylated derivatives (FTC-triphosphate (FTC-TP) and TFV-diphosphate (TFV-DP)) in plasma, peripheral blood mononuclear cells (PBMC), rectal tissue and fluid, and cervical tissue and cervicovaginal fluid, in a subset of participants (Tissue Subset).. 6) Assess changes in peripheral blood (all participants) and gut-associated lymphoid tissue (GALT) T cell phenotype (Tissue Subset). 7) Assess adherence in each of the four study arms as measured by an electronic medical device (EMD) and self-report. 8) Assess and characterize sexual behavior over time as measured by computer-assisted self-interview (CASI). 9) Assess the relationship between adherence and sexual risk-taking. 10) Evaluate the association of drug concentrations with other adherence measures. 11) Assess quality-of-life in each of the four study arms.