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

Abstract

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.

Methods: An 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 (Q4W) vs SoC (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 assessments 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. A subgroup analysis stratified by baseline third active drug class was performed.

Results: 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. Injections of CAB + RPV Q8W showed no significant differences across efficacy and safety outcomes versus daily oral SoC. Univariate subgroup analysis found there were no significant differences on virologic suppression or lack of virologic suppression for any baseline third active drug class subgroup. These results suggest that CAB + RPV Q8W is non-inferior to daily oral SoC.

Conclusions: This 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 registration: NCT02938520, NCT02951052, NCT03299049.

Keywords: Anti-HIV agents/administration and dosage; Anti-retroviral agents/therapeutic use; HIV infections/drug therapy; Indirect treatment comparison; Long-acting.

Conflict of interest statement

VC and NV are employees of ViiV Healthcare. SW is employee of GlaxoSmithKline and owns stocks/shares. SJS is an employee of Pharmerit– an OPEN Health Company, paid consultants to ViiV Healthcare.

© 2022. The Author(s).

Figures

Fig. 1

Diagram of studies included in indirect comparison. CAB cabotegravir, Q4W every 4 weeks, Q8W every 8 weeks, RPV rilpivirine, SoC standard of care, ATLAS/FLAIR antiretroviral therapy as long-acting suppression/first long-acting injectable regimen, ATLAS-2M antiretroviral therapy as long-acting suppression every 2 months

Fig. 2

Summary of risk difference results of the indirect comparison of CAB + RPV LA Q8W relative to SoC A by outcome, B virologic suppression (HIV RNA < 50 copies/mL as per FDA snapshot algorithm) results stratified by baseline third active drug class, and C lack of virologic suppression (HIV ≥ 50 copies/mL as per FDA Snapshot Algorithm) results stratified by baseline third active drug class. aFavors CAB + RPV Q8W. bMean difference. cValues could not be calculated for RR and OR as value for SoC in ATLAS/FLAIR was 0. AE adverse event, ATLAS/FLAIR antiretroviral therapy as long-acting suppression/first long-acting injectable regimen, CAB cabotegravir, CI confidence interval, HIV-1 human immunodeficiency virus type 1, INSTI integrase strand inhibitor, ISR injection-site reaction, LA Long-acting, NNRTI non-nucleoside reverse transcriptase inhibitor, OR Odds ratio, PI protease inhibitor, Q8W every 8 weeks, RNA ribonucleic acid, RPV rilpivirine, RR Relative risk, SoC standard of care