BACKGROUND: HPTN 083 is a Phase 2b/3 randomized multicenter double-blind, double-dummy, clinical trial evaluating safety and efficacy of long-acting injectable cabotegravir (CAB) compared to daily oral TDF/FTC for HIV PrEP. The blinded trial was stopped at a pre-planned interim DSMB review in May 2020.
METHODS: HIV-uninfected MSM and TGW at increased HIV risk were randomized 1:1 to either active CAB +TDF/FTC placebo (oral cabotegravir(CAB) for 5 weeks, then IM injections every 8 weeks for 148 weeks) or active TDF/FTC+CAB placebo (oral placebo for 5 weeks, then placebo injections on the same schedule). All participants were offered daily oral TDF/FTC for 48 weeks after last injection. The primary endpoints were incident HIV infection and grade 2 or higher clinical and laboratory events.
RESULTS: Participants were enrolled at 43 sites in Africa, Asia, Latin America, and the US (N=4566); median age: 26y (IQR 22-32); 12%TGW (n=567); 50% of US participants were Black (n=844). Participant retention at 6, 12, and 24 months was 91%, 87%, and 74%, respectively. Fifty-two incident HIV infections were observed over 6385 person-years, with overall HIV incidence 0.81% (95%CI 0.61-1.07); 39 infections were in the TDF/FTC arm (incidence 1.22%, 95%CI 0.87-1.67); 13 infections were in the CAB arm (incidence 0.41%, 95%CI 0.22-0.69%); HR: 0.34 (95%CI 0.18-0.62). Blinded study product injections covered 92% of person-years. Adherence to oral TDF/FTC was high; in a random subset of 372 TDF/FTC participants 87% had plasma samples with detectable concentrations, and 75% had concentrations consistent with daily dosing. CAB and TDF/FTC were both well tolerated; most adverse events were mild/moderate and balanced between arms. Injection site reactions, pyrexia, and hypertension were significantly more common in CAB participants, nausea was significantly more common in TDF/FTC participants. Injection intolerance led to discontinuation in 46 (2.2%) active CAB-LA recipients and was associated with the severity of the intolerance/reaction.
CONCLUSIONS: CAB and TDF/FTC were both safe and highly effective for PrEP in HPTN083, with estimated HIV incidence in the CAB arm 66% lower than in the TDF/FTC arm. CAB is the first injectable agent proven effective for HIV PrEP; a companion trial in cisgender women is ongoing.