Subcutaneous injections of cabotegravir plus rilpivirine long-acting in virally suppressed adults with HIV-1

Abstract

OBJECTIVE: To evaluate subcutaneous anterior abdominal injections of long-acting cabotegravir plus rilpivirine (CAB + RPV LA) in participants with more than 3 years' experience with intramuscular injections in the Phase 3 FLAIR (NCT02938520) study. DESIGN: Substudy of a phase 3, randomized, open-label, multicenter, noninferiority study. METHODS: Substudy phases included screening/intramuscular gluteal injection, subcutaneous injection [day 1-week (W) 8], and return to gluteal injection (W12-W20). The injection schedule was unchanged from the main study (every 4 weeks). Outcomes included pharmacokinetics, safety, tolerability, efficacy, and patient-reported outcomes. RESULTS: Overall, 93 participants were enrolled and received subcutaneous injections; 19% were female (sex at birth). CAB and RPV plasma exposures were generally comparable between subcutaneous and intramuscular injections, with 90% confidence intervals of geometric least squares mean ratios all within 0.80-1.25 boundary of no difference. Pain (48%), nodules (34%), and erythema (26%) were the most frequently reported subcutaneous-related injection site reactions (ISRs). Median durations of nodule and induration were longer with subcutaneous vs. intramuscular administration. Five (5%) participants withdrew due to a subcutaneous-related ISR. Few participants (2%) had HIV-1 RNA at least 50 copies/ml after subcutaneous injections. Participants reported greater pain and lower acceptability of ISRs following subcutaneous vs. intramuscular administration; 59% of participants preferred intramuscular injections. CONCLUSION: Pharmacokinetics and efficacy were similar between CAB+RPV LA subcutaneous and intramuscular administration; however, due to the higher incidence and duration of ISRs, along with lower tolerability and acceptability of subcutaneous injections, subcutaneous administration with the current CAB LA and RPV LA formulations is not being evaluated further.