HPTN 069

Study Purpose

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.

Study Design

Phase II, four-arm, multisite, randomized, double-blinded trial.

Study Population

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.

Study Size

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.

Study Duration

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).

Treatment Regime

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.

Primary Objectives

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.

Secondary Objectives

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.

Other Objectives