Long-Acting Injectable Cabotegravir + Rilpivirine for HIV Maintenance Therapy: Week 48 Pooled Analysis of Phase 3 ATLAS and FLAIR Trials

Abstract

Background: Long-acting (LA) injectable regimens are a potential therapeutic option in people living with HIV-1.

Setting: ATLAS (NCT02951052) and FLAIR (NCT02938520) were 2 randomized, open-label, multicenter, multinational phase 3 studies.

Methods: Adult participants with virologic suppression (plasma HIV-1 RNA <50 copies/mL) were randomized (1:1) to continue with their current antiretroviral regimen (CAR) or switch to the long-acting (LA) regimen of cabotegravir (CAB) and rilpivirine (RPV). In the LA arm, participants initially received oral CAB + RPV once-daily for 4 weeks to assess individual safety and tolerability, before starting monthly injectable therapy. The primary endpoint of this combined analysis was antiviral efficacy at week 48 (FDA Snapshot algorithm: noninferiority margin of 4% for HIV-1 RNA ≥50 copies/mL). Safety, tolerability, and confirmed virologic failure (2 consecutive plasma HIV-1 RNA ≥200 copies/mL) were secondary endpoints.

Results: The pooled intention-to-treat exposed population included 591 participants in each arm [28% women (sex at birth), 19% aged ≥50 years]. Noninferiority criteria at week 48 were met for the primary (HIV-1 RNA ≥50 copies/mL) and key secondary (HIV-1 RNA <50 copies/mL) efficacy endpoints. Seven individuals in each arm (1.2%) developed confirmed virologic failure; 6/7 (LA) and 3/7 (CAR) had resistance-associated mutations. Most LA recipients (83%) experienced injection site reactions, which decreased in incidence over time. Injection site reactions led to the withdrawal of 6 (1%) participants. The serious adverse event rate was 4% in each arm.

Conclusion: This combined analysis demonstrates monthly injections of CAB + RPV LA were noninferior to daily oral CAR for maintaining HIV-1 suppression.

FIGURE 1.

Study design and participant disposition. A, Study design. *Uninterrupted ART 6 months and VL <50 copies/mL at screening, 2 × VL <50 copies/mL ≤12 months (1 within the 6–12-month window, and 1 within 6 months prior to screening). †Optional switch to CAB + RPV LA at week 52 for those on CAR. ‡Participants received an initial loading dose of CAB LA (600 mg) and RPV LA (900 mg) at week 4. From week 8 onward, participants received CAB LA (400 mg) + RPV LA (600 mg) injections every 4 weeks. §The presence of any major INSTI or NNRTI resistance-associated mutation (except K103N) from prior genotype assay results were exclusionary. Figure adapted from Murray M, Antela A, Mills A, et al. Patient-Reported Outcomes in ATLAS and FLAIR Participants on Long-Acting Regimens of Cabotegravir and Rilpivirine Over 48 Weeks. AIDS Behav. 2020. https://doi.org/10.1007/s10461-020-02929-8, under a Creative Commons Attribution 4.0 International License, http://creativecommons.org/licenses/by/4.0/. 3TC, lamivudine; ABC, abacavir; CAB, cabotegravir; CAR, current antiretroviral therapy; DTG, dolutegravir; IM, intramuscular; HBsAg, hepatitis B surface antigen; PI, protease inhibitor; RAM, resistance-associated mutation; RPV, rilpivirine; VL, viral load. B, Participant disposition. *Participants who completed study participation at week 52 had the option to continue by entering the extension phase, transitioning to the ATLAS-2M study, or leaving the study (no withdrawal visit needed). The latter was not captured in this figure. ‡The remaining 65 participants in FLAIR were withdrawn from the study prior to randomization into the maintenance phase. CAR, current antiretroviral therapy; CAB, cabotegravir; RPV, rilpivirine.