The OUTCOMES Study is an evidence synthesis project involving ongoing systematic review of observational cohorts which describe virological outcomes among people transitioning to LA-CAB/RPV across different contexts (e.g., suppressed and non-suppressed). This article describes Phase 1 findings, which focused on people who are suppressed at time of LA-CAB/RPV initiation. 79 records met inclusion criteria for data extraction and analyses; for studies where virologic failure was not explicitly defined, investigators utilized another marker of VF (e.g., resistance or viral load exceeding a specified cut-off). Of the 79 studies which comprised 13,899 individuals overall, 172 experienced VF events across 48 studies. Genotypic data at VF were available for 28 studies, and out of the 80 VF events with available information, NNRTI DRMs were identified in 45 cases, INSTI DRMs in 40, and dual-class resistance in 33 (28 VF events had no evidence of resistance). The most prevalent NNRTI mutation was E138A/K (K101E/P/Q, K103K/R/N and Y181C/I were also noted), and the most prevalent INSTI mutations were Q148H/Q/K/R/S, E138A/E/K, G140G/S, L74L/M/I, T97T/A and R263K. Among 25 cohorts reporting post-VF regimens, PI-based combinations (31, 33.7%) were most commonly prescribed, followed by oral INSTI-based combinations (29, 31.5%). 27% (n=25) continued CAB/RPV after VF. Among 23 studies reporting re-suppression outcomes, re-suppression occurred in 87.8% (65/74).

Despite heterogeneity in virologic failure definitions, HIVDR information at failure, post-VF ART management details and follow-up duration, this analysis provides some reassurance that VF has remained uncommon among virologically suppressed people switching to LA-CAB/RPV in routine practice. However, among people experiencing VF on LA-CAB/RPV, emergent NNRTI and/or INSTI resistance was observed in over half of cases with available information. Although PI-based regimens were most commonly used after VF, oral INSTI-based combinations were prescribed in almost a third of cases and LA-CAB/RPV was continued in over a quarter. Overall, the majority of people with VF on LA-CAB/RPV resuppressed, although it should be noted that follow-up duration varied widely, and almost all studies included were based in high-income countries.