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. 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.

Implementation of long‐acting cabotegravir and rilpivirine: primary results from the perspective of staff study participants in the Cabotegravir And Rilpivirine Implementation Study in European Locations

“…In this Phase 3b, hybrid type III implementation–effectiveness trial carried out across diverse healthcare settings in five European countries, the implementation of CAB + RPV LA dosed Q2M was perceived as successful, regardless of implementation arm. In addition, for the clinical outcomes of the CARISEL study, CAB + RPV LA Q2M was found to be highly effective in maintaining virologic suppression, with a low rate of virologic failure [ 9 ]. The safety profile was also in line with previous findings.…”

“…The successful implementation in these, mostly LA‐naïve, clinics during the COVID‐19 pandemic is an encouraging sign as more providers adopt this new treatment modality. Additionally, the fact that 93% of all injections in CARISEL occurred within the ±7‐day dosing window, only one (0.23%, n = 1/430) patient study participant met the confirmed virological failure criterion, and 87% maintained virological suppression at Week 48 during peak waves of the COVID‐19 pandemic could also be considered a testament to the successful implementation of CAB + RPV LA [ 9 ].…”

“…For SSPs, CARISEL was designed as a two‐arm, unblinded study with centres randomized to either standard (Arm‐S) or enhanced (Arm‐E) implementation arms (Section 2.2 ). The study design has been previously published [ 9 ]. From each of the 18 clinics, four SSPs of various disciplines that play a crucial role in the delivery of care to PLWH (e.g.…”

“…Secondary implementation outcomes from the patient perspective will be the subject of a separate publication. The full clinical outcomes from the CARISEL study are available and have been published separately [ 9 ].…”