{"doi":"10.1093/cid/ciaf375","title":"Phase 2 Trial of Long-Acting Cabotegravir and VRC07-523LS for Viral Suppression in Adults With HIV-1: ACTG A5357","abstract":"BACKGROUND: Long-acting regimens are needed to expand antiretroviral therapy (ART) options for people with human immunodeficiency virus type 1 (HIV-1). Combining broadly neutralizing antibodies (bNAbs) with long-acting small-molecule antiretrovirals may offer an alternative to daily oral therapy. METHODS: We conducted a phase 2, open-label, single-arm trial at AIDS Clinical Trials Group (ACTG) sites across the United States. Eligible adults had HIV-1 virologically suppressed on ART for ≥2 years, CD4 count ≥350 cells/μL, and susceptibility to VRC07-523LS (half-maximal inhibitory concentration ≤0.25 µg/mL; inhibition >98%). Participants completed an oral cabotegravir (CAB) lead-in (Step 1), then received intravenous VRC07-523LS (40 mg/kg every 8 weeks) plus intramuscular CAB-LA (every 4 weeks) for 48 weeks (Step 2), followed by a return to standard ART (Step 3). Primary outcomes were treatment-related grade ≥3 adverse events (AEs), treatment discontinuation, and confirmed HIV-1 RNA ≥200 copies/mL by week 44. Virologic efficacy was assessed using Kaplan-Meier estimates. RESULTS: Seventy-four participants were enrolled (median age, 54 years; 26% female; 51% non-Hispanic White). Twelve (17%) experienced a primary safety event: 11 (15%) had grade ≥3 AEs, primarily transient infusion reactions, and 1 discontinued due to a grade 1 infusion event. The cumulative probability of virologic failure by week 44 was 7% (95% confidence interval, 3%-16%). One participant developed the R263K integrase resistance mutation. CONCLUSIONS: The VRC07-523LS plus CAB-LA regimen maintained viral suppression in 93% of participants, with only transient infusion reactions observed; however, instances of virologic breakthrough suggest that future studies should focus on optimizing efficacy outcomes. These results support continued investigation of bNAb-based long-acting ART combinations.","journal":"Clinical Infectious Diseases","year":2025,"id":521631,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9583,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1284905,"name":"Yu Zheng","orcid":"0000-0002-3542-6410","position":1,"is_corresponding":false},{"id":328574,"name":"Katherine Rodríguez","orcid":"0000-0001-9625-8839","position":2,"is_corresponding":false},{"id":394763,"name":"Leah Burke","orcid":"0000-0001-8220-3263","position":3,"is_corresponding":false},{"id":786360,"name":"Jacqueline D. 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