Phase 3 Trial of Weekly Oral Islatravir–Lenacapavir for HIV-1 Treatment

作者：Jürgen K. Rockstroh, Moti Ramgopal, Adrián Curran Fábregas, Malcolm Hedgcock, Kimberly Workowski, Sylvie Ronot-Bregigeon, Isabel Cassetti, Cynthia Brinson, Samir K. Gupta, Kuan‐Yin Lin, Mark O’Reilly, Jihad Slim, Hiroyuki Gatanaga, Peter Shalit, Shanyu Liu, Stephanie O. Klopfer, Fadi Shihadeh, Nidhi Patel, Renée-Claude Mercier, Melissa Shaughnessy, Hadas Dvory‐Sobol, Devi SenGupta, Cyril Llamoso, Martin S. Rhee, Chloe Orkin · 发表于：New England Journal of Medicine · 年份：2026 · DOI：10.1056/nejmoa2607973 · 被引用次数：4 · 研究领域：HIV/AIDS drug development and treatment、HIV Research and Treatment、HIV-related health complications and treatments

BACKGROUND: Once-daily, single-tablet regimens have transformed care for persons living with human immunodeficiency virus type 1 (HIV-1); however, challenges to adherence continue to limit effective treatment. Long-acting oral-drug combinations could offer new options with less frequent dose administration. METHODS: We conducted a phase 3, double-blind, randomized, active-controlled, noninferiority trial in 12 countries to evaluate the efficacy and safety of a switch to once-weekly oral islatravir-lenacapavir (ISL/LEN) from once-daily oral bictegravir-emtricitabine-tenofovir alafenamide (B/F/TAF) in adults in whom HIV-1 had been virologically suppressed for at least 6 months while they were receiving B/F/TAF. Participants were assigned in a 1:1 ratio to receive once-weekly ISL/LEN (2 mg/300 mg) or to continue once-daily B/F/TAF for 96 weeks; all received matched placebo for the alternative regimen. The primary end point was the percentage of participants with an HIV-1 RNA level of 50 copies per milliliter or higher at week 48, as determined by the Food and Drug Administration-defined snapshot algorithm. Noninferiority was determined at a margin of 4 percentage points. RESULTS: A total of 607 participants underwent randomization; 304 were assigned to the ISL/LEN group and 303 to the B/F/TAF group. A total of 21% of the participants were women, 31% were Black, 26% were Hispanic or Latine, and 15% were 65 years of age or older. At week 48, an HIV-1 RNA level of 50 copies per mil...