Phase 2 Trial of Long-Acting Cabotegravir and VRC07-523LS for Viral Suppression in Adults With HIV-1: ACTG A5357

作者：Babafemi Taiwo, Yu Zheng, Katherine Rodríguez, Leah Burke, Jacqueline D. Reeves, Kimberly K. Scarsi, Lúcio Gama, Christos J. Petropoulos, Pablo F. Belaunzarán-Zamudio, Paul Wannamaker, Ronald D’Amico, Parita Rathod, Katharine J. Bar, Pablo Tebas, for the A5357 Study Team, Stephen Wolfe, Chad J. Achenbach, William R. Short, Su Kyung Kim, Edgar T. Overton, Michael Messer, Carl J. Fichtenbaum, Sarah Trentman, Stephanie Solso, Constance A. Benson, Magdalena E. Sobieszczyk, Anyelina Cantos, Elizabeth R. Duke, Eli Burnham, Charles Flexner, Rebecca L Becker, Raghd Alyatim, Teresa Spitz, Vanessa Sutton, Joslyn Axinn, Suzanne Hendler, Azquena Munoz Lopez, Sonal S. Munsiff, Susan E. Hulse, David A. Wohl, Erin Hoffman, Rebecca C. Fry, Jessenia Fuentes, Susan L. Koletar, Heather Harber, Amesika N. Nyaku, ChristieLyn Costanza, Jorge L. Santana Bagur, Sigrid Pérez-Frontera, Shaun Barcavage, Todd Stroberg · 发表于：Clinical Infectious Diseases · 年份：2025 · DOI：10.1093/cid/ciaf375 · 被引用次数：5 · 研究领域：HIV/AIDS drug development and treatment、HIV Research and Treatment、HIV/AIDS Research and Interventions

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 in...