Comparable real-world effectiveness between switches to cabotegravir + rilpivirine long-acting or modern daily oral regimens in the United States: an OPERA cohort study.

INTRODUCTION: Cabotegravir + rilpivirine long-acting (CAB+RPV LA) injectable was approved in the United States in 2021 for HIV-1 treatment in virologically suppressed (viral load [VL] <50 copies/mI individuals. In clinical trials, CAB+RPV LA was non-inferior to oral antiretroviral therapy (ART) regimens in virologically suppressed individuals. We compared real-world effectiveness between CAB+RPV LA and oral ART regimens and assessed predictors of confirmed virologic failure (CVF) on CAB+RPV LA. METHODS: From the OPERA® cohort, ART-experienced, virologically suppressed adults with HIV switching to CAB+RPV LA or a new oral ART regimen between 21 January 2021 and 31 December 2022 were followed through 30 June 2023. CVF was defined as 2 VL ≥200 copies/ml or 1 VL ≥200 copies/ml + discontinuation. Logistic regression was used to assess CVF risk by regimen and CVF predictors among CAB+RPV LA users. RESULTS: During the study period, 1362 virologically suppressed adults switched to CAB+RPV LA, and 2783 switched to a new oral ART regimen (92% second-generation integrase inhibitor [INSTI]-based). Compared to oral ART users, CAB+RPV LA users were younger, on their prior regimen less time and more likely to switch from an INSTI; median CD4 counts at initiation were similar. At study end, 81% of CAB+RPV LA users and 80% of oral ART users were on their respective regimens. CVF risk with CAB+RPV LA did not statistically differ compared to oral ART (adjusted odds ratio: 0.64; 95% confidence interval [CI]: 0.34, 1.14). Among CAB+RPV LA users, only baseline CD4 predicted CVF; every 100 CD4 cells/µl increase was associated with 20% lower CVF risk (OR [95% CI]: 0.80 [0.64, 0.97]). CONCLUSIONS: In the United States, routine clinical care, CVF risk did not differ between a switch to CAB+RPV LA or new oral ART, with most individuals remaining on their regimens at study end. Lower CD4 count at initiation was the only predictor of CVF on CAB+RPV LA.