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Long acting injectable cabotegravir is safe and effective in preventing HIV infection in cisgender women: interim results from HPTN 084

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BACKGROUND: HPTN 084 is a Phase 3 randomized, double-blind, double-dummy superiority trial evaluating safety and efficacy of long-acting injectable cabotegravir (CAB) compared to daily oral TDF/FTC for HIV prevention in cisgender women. The blinded trial was stopped at a planned interim DSMB review in November 2020.
METHODS: HIV-uninfected PrEP eligible cisgender women were randomized 1:1 to either active CAB plus TDF/FTC placebo or active TDF/FTC plus CAB placebo. Participants received 5 weeks of daily oral product followed by intramuscular injections every 8 weeks after an initial 4-week interval load, alongside daily oral pills. Participants who discontinued injections were offered open-label daily TDF/FTC for 48 weeks after last injection. The primary endpoints were incident HIV infection and '┬ągrade 2 clinical and laboratory events.
RESULTS: Overall, 3224 participants were enrolled at sites in South Africa (n=7), Zimbabwe (5), Uganda (3), Malawi (2), Botswana (1), Eswatini (1) and Kenya (1). Median age was 25 years (range 18, 45), 54% (n=1754/3210) had 2+ partners in past month, 32% (n=1019/3210) had partner with HIV or unknown status, 19% (n=601/3190) had chlamydia and 7% (n=211/3190) had gonorrhoea at enrolment. Participant visit completion at months 6, 12, 18, and 24 was 94%, 90%, 87% and 86%. Thirty eight incident infections were observed over 3808 person-years (HIV incidence 1.0%, 95% confidence interval [CI] 0.71, 1.37); 4 in the CAB arm (incidence 0.21, 95% CI 0.06, 0.54) and 34 in the TDF/FTC arm (incidence 1.79%, 95% CI 1.24, 2.51) (hazard ratio 0.11 (95% CI 0.04, 0.32)). Injection coverage was 93% of person-years. In a random subset of 375 TDF/FTC participants, 62% of plasma samples had detectable TDF/FTC; 46% had concentrations consistent with daily dosing. Adverse events were mild-moderate and balanced by arm. Among CAB participants, injection site reactions were more common (32% vs. 9%), but most were mild. Nausea was more common in the TDF/FTC (9%) compared to the CAB participants (5%). Pregnancy incidence was 1.3 per 100 person-years (95% CI 1.0, 1.7); no congenital anomalies were reported.
CONCLUSIONS: While both products demonstrated high prevention efficacy and were safe and well tolerated; CAB was superior to TDF/FTC in preventing HIV infection in cisgender women.