Evaluating the Safety and Efficacy of Long-Acting Injectable Cabotegravir Compared to Daily Oral TDF/FTC for Pre-Exposure Prophylaxis in HIV-Uninfected Women


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Primary Outcome Measures:

  • Number of documented incident HIV infections in Steps 1 and 2 [ Time Frame: Measured through Week 81 ]

    HIV incidence rate will be calculated as the total number of participants with confirmed incident HIV infection during study follow-up of Step 1 and Step 2 divided by the person-years accumulated in each arm.

  • Number of Grade 3 or higher clinical and laboratory adverse events (AEs) [ Time Frame: Measured through participant’s last study visit, up to 4.6 years after study entry, depending on when they enroll in the study ]

    AEs will be summarized using MedDRA System Organ Class and preferred terms.

Secondary Outcome Measures:

  • Number of documented incident HIV infections in participants in subgroups broken down by baseline age [ Time Frame: Measured through participant’s last study visit, up to 4.6 years after study entry, depending on when they enroll in the study ]

    For each of the specified baseline factors, a Cox proportional hazards model will be fit with treatment arm, baseline factor and their interaction as covariates, stratified by site.

  • Number of documented incident HIV infections in participants in subgroups broken down by baseline HSV-2 status [ Time Frame: Measured through participant’s last study visit, up to 4.6 years after study entry, depending on when they enroll in the study ]

    For each of the specified baseline factors, a Cox proportional hazards model will be fit with treatment arm, baseline factor and their interaction as covariates, stratified by site.

  • Number of documented incident HIV infections in participants in subgroups broken down by baseline contraceptive use method [ Time Frame: Measured through participant’s last study visit, up to 4.6 years after study entry, depending on when they enroll in the study ]

    For each of the specified baseline factors, a Cox proportional hazards model will be fit with treatment arm, baseline factor and their interaction as covariates, stratified by site.

  • Number of documented incident HIV infections in participants in subgroups broken down by baseline body mass index (BMI) less than/greater than or equal to 25 kg/m^2 [ Time Frame: Measured through participant’s last study visit, up to 4.6 years after study entry, depending on when they enroll in the study ]

    For each of the specified baseline factors, a Cox proportional hazards model will be fit with treatment arm, baseline factor and their interaction as covariates, stratified by site.

  • Plasma and dried blood spot (DBS) levels of CAB in participants randomized to CAB/CAB LA [ Time Frame: Measured through participant’s last study visit, up to 4.6 years after study entry, depending on when they enroll in the study ]

    Plasma and DBS samples for drug concentrations will be collected throughout the study from all participants, although PK testing may be limited to a subset of the samples.

  • Plasma levels of tenofovir/tenofovir diphosphate (TFV/TFV-DP) in participants randomized to TDF/FTC [ Time Frame: Measured through participant’s last study visit, up to 4.6 years after study entry, depending on when they enroll in the study ]

    Plasma samples for drug concentrations will be collected throughout the study from all participants, although PK testing may be limited to a subset of the samples.

  • Number of participants willing to use CAB LA and TDF/FTC [ Time Frame: Measured through participant’s last study visit, up to 4.6 years after study entry, depending on when they enroll in the study ]

    Assessed through administration of brief behavioral surveys.

The purpose of this study is to evaluate the safety and efficacy of the long-acting injectable integrase inhibitor cabotegravir (CAB LA) compared to daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) for pre-exposure prophylaxis (PrEP) in a population of sexually active HIV-uninfected women at risk for HIV.

This study will take place in three steps. Participants will be randomly assigned to one of two arms:

Arm A:

Step 1: Participants will receive daily oral CAB and TDF/FTC placebo for 5 weeks.

Step 2: Participants will receive injections of CAB LA at two time points 4 weeks apart and every 8 weeks thereafter and daily TDF/FTC placebo beginning at Week 5.

Arm B:

Step 1: Participants will receive daily TDF/FTC and oral CAB placebo for 5 weeks.

Step 2: Participants will receive daily TDF/FTC and intramuscular (IM) placebo injections at two time points 4 weeks apart and every 8 weeks thereafter beginning at Week 5.

Step 2 will continue until the last enrolled participant reaches approximately 76 weeks on Step 2 (Week 81 for the last enrolled participant).

In Step 3, all participants (Arms A and B) will receive daily TDF/FTC for up to 48 weeks, starting no later than 8 weeks after the last injection.

At the end of Step 3, all participants will then transition to locally available HIV prevention services, including services for PrEP, if available.

Study visits will occur at Day 0 and at Weeks 2 and 4 during Step 1. During Step 2, participants will attend up to 24 visits, depending on when they enroll in the study. Study visits will occur every 12 weeks during Step 3. Study visits may include physical examinations; blood, urine, and vaginal swab collection; and risk reduction and adherence counseling.