The HIV Prevention Trials Network (HPTN) 083 study comparing the efficacy and safety of investigational, long-acting, injectable cabotegravir (ViiV Healthcare) to daily oral emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) (Truvada; Gilead Sciences) for HIV prevention was stopped early after the trial achieved the primary end point of noninferiority with the difference approaching superiority for cabotegravir. The study is jointly funded by National Institute of Allergy and Infectious Diseases (NIAID) and ViiV Healthcare.
The global, controlled, double-blind phase 2b/3 study included 4570 cisgender men and transgender women who have sex with men. Two-thirds of the patients were under 30 years of age, and 12% were transgender women. Patients were randomized to receive either cabotegravir intramuscularly every 8 weeks or FTC/TDF tablets (200mg/300mg) for pre-exposure prophylaxis (PrEP) orally daily for up to a maximum of 3 years; each participant received 1 active drug and 1 placebo in order to maintain the blinded part of the study.
Interim analysis showed that cabotegravir was found to be 69% (95% CI 41%-84%) more effective than FTC/TDF in preventing HIV acquisition among the study population. A total of 50 incident HIV infections occurred in the trial, of which 12 infections occurred in the cabotegravir arm with an HIV incidence rate of 0.38% (95% CI, 0.20-0.66) and 38 infections in the FTC/TDF arm with an HIV incidence rate of 1.21% (95% CI, 0.86-1.66). The hazard ratio in the cabotegravir arm compared with the FTC/TDF arm was 0.31 (nominal 95% CI, 0.16-0.59).
The safety profile in both groups was similar with 80% of patients in the cabotegravir arm reporting pain or tenderness at the injection site vs 31% of those in the FTC/TDF arm who received placebo injections. Patients in the cabotegravir arm also reported a 2% discontinuation rate due to injection site reactions or injection intolerance vs 0% in the FTC/TDF arm.
The decision to stop the trial was made based on the recommendation from the study’s independent Data and Safety Monitoring Board (DSMB). Full detailed results will be presented at an upcoming scientific meeting and will be used for future regulatory submissions.
“Demonstrating conclusively that long-acting injectable cabotegravir is highly effective almost 2 years earlier than originally expected is exciting news,” said HPTN 083 protocol chair Raphael J. Landovitz, MD, MSc. “It is inspiring that we may soon have additional HIV prevention options for at-risk individuals who have difficulty with or prefer not to take pills.”
The phase 3 HPTN 084 study comparing the efficacy and safety of cabotegravir to oral FTC/TDF tablets for HIV prevention among women in sub-Saharan Africa will continue as planned following the DSMB recommendation.
For more information visit hptn.org.