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

Date: 
5/6/24
Citation: 

Jonsson-Oldenbüttel, Celia MDa,b; Ghosn, Jade MD, PhDc,d; van der Valk, Marc MD, PhDe; Florence, Eric MD, PhDf; Vera, Francisco MD, PhDg; De Wit, Stéphane MDh; Rami, Agathe MDi; Bonnet, Fabrice MD, PhDj; Hocqueloux, Laurent MDk; Hove, Kai MResl; Ait-Khaled, Mounir PhDl; DeMoor, Rebecca MScm; Bontempo, Gilda MDn; Latham, Christine L. MSn; Gutner, Cassidy A. PhDn; Iyer, Supriya MSco; Gill, Martin BScp; Czarnogorski, Maggie MD, MPHn; D’Amico, Ronald DO, MScn; van Wyk, Jean MBChBl. Safety and Effectiveness From the CARISEL Study: Phase 3b Hybrid Type III Implementation Study Integrating Cabotegravir + Rilpivirine Long-Acting Into European Clinical Settings. JAIDS Journal of Acquired Immune Deficiency Syndromes ():10.1097/QAI.0000000000003448, May 06, 2024. | DOI: 10.1097/QAI.0000000000003448

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.