Outcomes of real-world initiation of long-acting injectable cabotegravir and rilpivirine (LA-I CAB + RPV) in individuals with viraemia: A systematic review of baseline characteristics, virological failure outcomes and discontinuations

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Elias,Alexa;Pasin,Chloé;Smuk,Melanie;Paterson,Amy;Orkin,Chloe M.

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2025

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BACKGROUND: When using long-acting injectable cabotegravir and rilpivirine (CAB + RPV) in individuals with viraemia, beyond small cohorts, little is known about baseline characteristics, virological failure outcomes, resistance emergence, re-suppression and discontinuation. METHODS: We identified evidence from PubMed, EMBASE, Cochrane and conference abstract databases through 17 March 2025 to synthesize data from observational cohort studies (OCS) that reported on virological failure (VF) events in individuals with viraemia at initiation of LA-I CAB + RPV. We extracted data on baseline clinical and socio-demographic characteristics, VF, resistance-associated mutations (RAMs) at VF, post-VF regimen choice, re-suppression and discontinuation. RESULTS: Across 14 cohorts including 561 individuals, there were 36 VF events (OCS-level VF rate 0% (n/N = 0/12, 0/12 and 0/10) to 25% (n/N = 3/12)). VF definitions varied. 6/14 OCS (n = 436) reported on baseline CD4 count, 13/14 (n = 543) on baseline viral load and 7/14 (n = 459) on socio-demographic characteristics. Among the 14 VF events with genotypic information available at VF, NNRTI RAMs were identified in 13/14 individuals, INI RAMs in 9/14 and dual-class resistance in 8/14 individuals. Post-VF regimens were reported for 16/36 individuals with VF and included lenacapavir (LEN)-based regimens, protease inhibitor (PI)-based regimens or LA-I CAB + RPV continuation. Re-suppression outcomes were described in 10 VF events: re-suppression occurred in 5/10. CONCLUSIONS: In OCS, the follow-up duration was short and VF definitions were highly variable, with few cohorts reporting VF outcomes in people with baseline VL >10 000 c/mL. VF was frequently accompanied by resistance. Post-VF regimens varied, and their success was unclear due to the small sample size.

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HIV medicine

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