{"doi":"10.1093/cid/ciae631","title":"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. 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.","journal":"Clinical Infectious Diseases","year":2024,"id":423996,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":23,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9481,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1220335,"name":"Cameron T. Nutt","orcid":null,"position":1,"is_corresponding":false},{"id":69650,"name":"Mark J. Siedner","orcid":"0000-0003-3506-842X","position":2,"is_corresponding":false},{"id":584834,"name":"Suzanne M. McCluskey","orcid":"0000-0001-8463-5430","position":3,"is_corresponding":false},{"id":295301,"name":"Andrew Hill","orcid":"0000-0002-6494-7645","position":4,"is_corresponding":false},{"id":1219870,"name":"Andrea Perez Navarro","orcid":"0000-0002-9816-4032","position":0,"is_corresponding":true}],"reference_count":56,"raw_metadata":null,"created_at":"2026-07-19T01:58:01.889748Z","pmid":"39724249","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}