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

Abstract

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. In this study, we report month 12 clinical outcomes in patient study participants (PSPs) in the CAB and RPV Implementation Study in European Locations (CARISEL) study.

Setting: CARISEL is a phase 3b implementation-effectiveness study.

Methods: CARISEL was designed as a 2-arm, unblinded study with centers randomized to either enhanced or standard implementation arms. For PSPs, this 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 and <50 copies/mL (Snapshot algorithm), incidence of confirmed virologic failure (CVF; 2 consecutive plasma HIV-1 RNA levels ≥200 copies/mL), adherence to injection visit windows, and safety and tolerability.

Results: Four hundred thirty PSPs were enrolled and treated; the mean age was 44 years (30% ≥50 years), 25% were women (sex at birth), and 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, the 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.

Trial registration: ClinicalTrials.gov NCT04399551.

FIGURE 1.

Study design. *Four hundred thirty-seven PSPs enrolled, and 430 received CAB + RPV LA. ^†Dose 1 was received at month 1, dose 2 at month 2, with the remaining doses Q2M thereafter. ^‡Introduce CAB + RPV LA to clinic staff and discuss what might make implementation easier and/or what might make it difficult before the first injection at the site. Meetings discussed implementation plans, how to work through challenges, and how to introduce continuous quality improvement. Arm-E, enhanced implementation arm; Arm-S, standard implementation arm; CQI, continuous quality improvement; MSL, medical scientific liaison; OLI, oral lead-in; SWAT, skilled wrap-around team.

FIGURE 2.

Randomization and treatment*. *A single PSP may have more than 1 reason for withdrawal/failure. ^†Includes 1 participant who was reclassified as discontinuing due to an AE before month 12, after the primary analysis was completed. ^‡Completed the intervention phase (month 12). Arm-E, enhanced implementation arm; Arm-S, standard implementation arm.