Indirect comparison of 48-week efficacy and safety of long-acting cabotegravir and rilpivirine maintenance every 8 weeks with daily oral standard of care antiretroviral therapy in participants with virologically suppressed HIV-1-infection

Background: Efficacy and safety of long-acting cabotegravir (CAB) + rilpivirine (RPV) every 8 weeks (Q8W) versus daily oral standard of care (SoC) maintenance in treatment-experienced individuals with virologically suppressed human immunodeficiency virus type 1 (HIV-1) has not been directly compared in randomized clinical trials. This analysis aimed to indirectly compare these regimens. MethodsAn adjusted indirect treatment comparison of CAB + RPV Q8W with daily oral SoC was performed, using Phase 3 data from studies of CAB + RPV every 4 weeks vs SoC (Q4W; ATLAS/FLAIR, n=591 per group) and a Phase 3b trial of CAB + RPV Q8W vs Q4W (ATLAS-2M [excluding participants with prior CAB + RPV exposure]; n=327 per group). Eligible participants were virologically suppressed (viral load <50 HIV-1 ribonucleic acid (RNA) copies/mL), treatment-experienced individuals with HIV-1-infection. Treatment efficacy and safety at Week 48 included virologic suppression and lack of virologic suppression (proportion of participants with plasma HIV-1 RNA <50 copies/mL or ≥50 copies/mL, respectively; both as per FDA snapshot algorithm), CD4-cell count change from baseline, no virologic data, discontinuations due to adverse events (AEs), and overall AEs, serious AEs and Grade 3–5 AEs excluding injection-site reactions. Baseline characteristics between the Q4W arms of ATLAS/FLAIR and ATLAS-2M showed no significant differences or differences were not judged to be clinically relevant, apart from participants switching from a baseline third active drug class; more participants switched from integrase strand inhibitors in ATLAS/FLAIR, and from non-nucleoside reverse transcriptase inhibitors in ATLAS-2M. A subgroup analysis stratified by baseline third active drug class was performed. ResultsInjections of CAB + RPV Q8W showed no significant differences across efficacy and safety outcomes versus daily oral SoC. The subgroup analysis found there were no significant differences on virologic suppression or lack of virologic suppression for any baseline third active drug class subgroups. These results suggest that CAB + RPV Q8W is non-inferior to daily oral SoC.ConclusionsThis analysis supports the therapeutic potential of CAB + RPV Q8W for virologically suppressed people living with HIV-1 infection seeking an alternative maintenance treatment option to daily oral SoC.Trial registrationNCT02938520, NCT02951052, NCT03299049