Safety and Effectiveness From the CARISEL Study: Phase 3b Hybrid Type III Implementation Study Integrating Cabotegravir + Rilpivirine Long-Acting Into European Clinical Settings

Background: Cabotegravir + rilpivirine long-acting (CAB + RPV LA) dosed every 2 months (Q2M) is a complete regimen for the maintenance of HIV-1 virologic suppression. Here, we report Month 12 clinical outcomes in patient study participants (PSPs) in the CARISEL study. Setting: CARISEL is a Phase 3b implementation–effectiveness study. Methods: CARISEL was designed as a two-arm, unblinded study with centers randomized to either enhanced or standard implementation arms. For PSPs, the study is single arm, unblinded, and interventional; all PSPs switched from daily oral therapy to CAB + RPV LA dosed Q2M. The primary objective was to evaluate the perceived acceptability, appropriateness, and feasibility of CAB + RPV LA implementation for staff participants (presented separately). Clinical secondary endpoints assessed through Month 12 included: the proportion of PSPs with plasma HIV-1 RNA ≥50 copies/mL and <50 copies/mL (Snapshot algorithm), incidence of confirmed virologic failure (CVF; two consecutive plasma HIV-1 RNA levels ≥200 copies/mL), adherence to injection visit windows, and safety and tolerability. Results: 430 PSPs were enrolled and treated; mean age was 44 years (30% ≥50 years), 25% were female (sex at birth), 22% were persons of color. At Month 12, 87% (n=373/430) of PSPs maintained HIV-1 RNA <50 copies/mL, with 0.7% (n=3/430) having HIV-1 RNA ≥50 copies/mL. One PSP had CVF. The safety profile was consistent with previous findings. Overall, results were similar between implementation arms. Conclusion: CAB + RPV LA Q2M was well tolerated and highly effective in maintaining virologic suppression with a low rate of virologic failure.