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

To evaluate subcutaneous (SC) anterior abdominal injections of long-acting cabotegravir plus rilpivirine (CAB+RPV LA) in participants with >3 years' experience with intramuscular (IM) injections in the Phase 3 FLAIR (NCT02938520) study. Substudy of a Phase 3, randomized, open-label, multicenter, noninferiority study. Substudy phases included screening/IM gluteal injection, SC 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. Overall, 93 participants were enrolled and received SC injections; 19% were female (sex at birth). CAB and RPV plasma exposures were generally comparable between SC and IM 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 SC-related injection site reactions (ISRs). Median durations of nodule and induration were longer with SC vs. IM administration. Five (5%) participants withdrew due to an SC-related ISR. Few participants (2%) had HIV-1 RNA ≥50 copies/mL after SC injections. Participants reported greater pain and lower acceptability of ISRs following SC vs. IM administration; 59% of participants preferred IM injections. Pharmacokinetics and efficacy were similar between CAB+RPV LA SC and IM administration; however, due to the higher incidence and duration of ISRs, along with lower tolerability and acceptability of SC injections, SC administration with the current CAB LA and RPV LA formulations is not further being evaluated.