Virologic Failure and Emergent Integrase Strand Transfer Inhibitor Drug Resistance With Long-Acting Cabotegravir for HIV Treatment: A Meta-analysis

Abstract Background The long-acting injectable regimen of cabotegravir plus rilpivirine (CAB/RPV) emerged as an alternative to oral standard-of-care integrase strand transfer inhibitor (INSTI)–based regimens for individuals with adherence challenges or preference for reduced dosing schedules. Althou...

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Veröffentlicht in:Clinical infectious diseases Jg. 81; H. 2; S. 274 - 285
Hauptverfasser: Perez Navarro, Andrea, Nutt, Cameron T, Siedner, Mark J, McCluskey, Suzanne M, Hill, Andrew
Format: Journal Article
Sprache:Englisch
Veröffentlicht: US Oxford University Press 16.09.2025
Schlagworte:
Anti-HIV Agents - therapeutic use
Diketopiperazines
Drug Resistance, Viral
HIV Infections - drug therapy
HIV Infections - virology
HIV Integrase Inhibitors - administration & dosage
HIV Integrase Inhibitors - pharmacology
HIV Integrase Inhibitors - therapeutic use
HIV-1 - drug effects
HIV-1 - genetics
Humans
Pyridones - administration & dosage
Pyridones - therapeutic use
Rilpivirine - administration & dosage
Rilpivirine - therapeutic use
Treatment Failure
Viral Load - drug effects
drug resistance
HIV
cabotegravir
antiretroviral therapy
integrase strand trasfer inhibitors
ISSN:1058-4838, 1537-6591, 1537-6591
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Zusammenfassung:Abstract Background The long-acting injectable regimen of cabotegravir plus rilpivirine (CAB/RPV) emerged as an alternative to oral standard-of-care integrase strand transfer inhibitor (INSTI)–based regimens for individuals with adherence challenges or preference for reduced dosing schedules. Although oral INSTI regimens have a high barrier to emergent resistance, less is known about the potency and durability of CAB/RPV. Methods We reviewed clinical trial registries, PubMed, EMBASE, and conference abstract databases to identify reports of CAB/RPV for HIV therapy. We abstracted data on virologic failure (VF) and treatment-emergent INSTI resistance at 48 weeks (range: 24–52). We used single-proportion meta-analysis to summarize outcomes in 3 populations: antiretroviral therapy (ART)–naive individuals initiating CAB/RPV following suppression on oral ART, ART-experienced individuals switched to CAB/RPV with virologic suppression, and ART-experienced individuals switched to CAB/RPV with detectable viremia. Cochrane's RoB 2.0 and ROBINS-1 tools assessed risk of bias. Results Thirty-three studies (N = 9224) reported VF prevalence. Nineteen studies (N = 5662) reported resistance data. VF prevalence was 1% (95% CI: 1%–3%) in induction-maintenance studies, 1% (1%–2%) in switch-suppressed studies, and 5% (3%–10%) in switch-viremic studies. INSTI resistance prevalence among successfully genotyped participants at failure was 71% (25%–95%), 61% (44%–75%), and 41% (20%–65%) respectively. Dolutegravir cross-resistance was common (64% of those with emergent resistance). Conclusions Although VF rates with CAB/RPV were low, INSTI resistance emerged in approximately 40%–70% of individuals experiencing VF. These rates are significantly higher than those for oral INSTI-based regimens. Both individual-level and broader resistance surveillance may be warranted in populations with expanding CAB/RPV use. Clinical Trials Registration. PROSPERO registration CRD42024543919. Although 48-week virological failure rates were low, emergent integrase resistance among those failing injectable cabotegravir was common (41%–71%), and cross-resistance with dolutegravir was high. Surveillance of resistance after cabotegravir failure may be critical to ensure sustainability of dolutegravir-based antiretroviral therapy. Graphical Abstract Graphical Abstract This graphical abstract is also available at Tidbit: https://tidbitapp.io/institutional-portal/clinical-infectious-diseases/tidbits/virologic-failure-and-emergent-integrase-strand-transfer-inhibitor-drug-resistance-with-long-acting-cabotegravir-for-hiv-treatment-a-meta-analysis/update
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ISSN:1058-4838
1537-6591
1537-6591
DOI:10.1093/cid/ciae631