RELEVANCE: PrEP agents are needed that do not depend on daily or near-daily pill-taking. The development of alternative agents for PrEP, and/or more adherence-friendly schedules for currently available agents, could increase prevention choices and increase acceptability. Long-acting injectable agents have the potential to prevent HIV acquisition without relying on adherence to a daily oral regimen.
DESCRIPTION: Once randomized to one of two arms, participants will move through the steps below and followed for up to 4 and a half years:
Arm A – Daily oral CAB (30 mg tablets) and oral TDF/FTC placebo for five weeks
Arm B – Daily oral TDF/FTC (300 mg/200 mg fixed-dose combination tablets) and oral CAB placebo for five weeks
A participant that becomes HIV-infected during Step 1 of the study will permanently discontinue study product and will be terminated from the study, and referred for HIV-related care.
Arm A – CAB LA (600 mg as a single intramuscular [IM] injection at two time points 4 weeks apart and every 8 weeks thereafter) and daily oral TDF/FTC placebo.
Arm B – Daily oral TDF/FTC (300/200 mg fixed-dose combination tablets) and IM placebo at two time points 4 weeks apart and every 8 weeks thereafter (matching vehicle, identical volume as active injectable product in Arm A).
This step will continue until the required number of endpoints is reached.
A participant that becomes HIV-infected during Step 2 of the study will permanently discontinue study product, be placed on immediate suppressive ART, and be followed for 52 weeks after their last injection, after which their participation in the study will end and they will be transitioned to continued HIV-related care.
Both arms: Open-label daily oral TDF/FTC no later than 8 weeks after the last injection (in order to cover the pharmacokinetic (PK) tail for Arm A participants), for up to 48 weeks.
Participants will then transition to locally-available HIV prevention services, including services for PrEP, if available.
A participant with confirmed HIV infection during Step 3 will be followed at least for the duration of Step 3.
STATUS: This study is currently active, but closed to enrollment.