Final efficacy and safety of twice-yearly subcutaneous lenacapavir in treatment-naive people with HIV

作者：Debbie Hagins, Mezgebe Berhe, Gordon Crofoot, Moti Ramgopal, James J. Sims, Cheryl McDonald, Peter Ruane, William E. Sanchez, Anita Scribner, Paul Benson, Shanyu Liu, Laurie A. VanderVeen, Hadas Dvory‐Sobol, Martin S. Rhee, Samir K. Gupta · 发表于：AIDS · 年份：2025 · DOI：10.1097/qad.0000000000004372 · 被引用次数：5 · 研究领域：HIV/AIDS drug development and treatment、HIV Research and Treatment、HIV-related health complications and treatments

OBJECTIVE: To assess final efficacy (through Week [W] 132), safety, and emergent resistance with lenacapavir-based combination regimens in the CALIBRATE study. DESIGN: CALIBRATE was a Phase 2, randomized, open-label study (NCT04143594). METHODS: Treatment-naive PWH were randomized (2 : 2:2 : 1) to four treatment groups (TG): TG1 and TG2 received twice-yearly subcutaneous lenacapavir plus oral daily emtricitabine/tenofovir alafenamide (F/TAF); TG3 received oral daily lenacapavir plus F/TAF; and TG4 received oral daily bictegravir/F/TAF. At W28, TG1 switched to lenacapavir plus TAF and TG2 switched to lenacapavir plus bictegravir. At W80, TG4 completed the study and TG1-3 continued assigned treatments. RESULTS: Overall, 182 participants received at least one dose of study drug (TG1-4, respectively: n = 52, n = 53, n = 52, n = 25). Virologic suppression (HIV-1 RNA <50 copies/ml) at W80 by FDA snapshot: 87, 75, 87, and 92% in TG1-4, respectively. When excluding missing data, virologic suppression at W132 across TG1-3 was 98-100%. Mean (95% CI) increase from baseline to W80 in CD4 cells/μl was consistent across TG1-4: 275 (214; 337), 262 (203; 320), 245 (174; 315), and 248 (155; 340), respectively. No serious treatment-related adverse events occurred. Two participants in TG1 and three in TG2 discontinued study drug due to adverse events. Injection-site reactions were mostly mild to moderate. LEN resistance-associated mutations emerged in four participants. CONCLUSION: Lenacapavir-...