Leronlimab Treatment for Multidrug-Resistant HIV-1 (OPTIMIZE): A Randomized, Double-Blind, Placebo-Controlled Trial

作者：Joseph Gathe, Edwin DeJesus, Moti Ramgopal, Charlotte-Paige Rolle, Otto O. Yang, William E. Sanchez, Jacob Lalezari, Alok Krishen, Jonah B. Sacha, Scott G. Hansen, Joseph Meidling · 发表于：JAIDS Journal of Acquired Immune Deficiency Syndromes · 年份：2025 · DOI：10.1097/qai.0000000000003648 · 被引用次数：6 · 研究领域：HIV Research and Treatment、HIV/AIDS drug development and treatment、Viral-associated cancers and disorders

BACKGROUND: Leronlimab is a humanized κ-IgG4 monoclonal antibody that blocks C-C chemokine receptor type 5. We investigated leronlimab as a treatment option for people living with multidrug-resistant HIV-1. SETTING AND METHODS: In a phase 2b/3, multicenter, randomized, double-blind, placebo-controlled study conducted in 21 hospital centers in the United States, treatment-experienced people living with HIV with documented drug resistance were randomly assigned once weekly leronlimab (350 mg subcutaneously) or matching placebo for 1 week overlapping existing failing antiretroviral therapy, followed by a 24-week single-arm extension with weekly leronlimab combined with a new optimized background treatment. The primary end point was achieving ≥0.5 log 10 reduction in plasma HIV-1 RNA from baseline at the end of the 1-week double-blinded treatment period. RESULTS: Fifty-two participants were enrolled (25 leronlimab and 27 placebo). After the 1-week randomized phase, by the intent-to-treat analysis, 64.0% (16/25) receiving leronlimab achieved ≥0.5 log 10 reduction in plasma HIV-1 RNA versus 23.1% (6/26) receiving placebo ( P = 0.0032), whereas by per protocol analysis, 72.7% (16/22) receiving leronlimab achieved ≥0.5 log 10 reduction in plasma HIV-1 RNA versus 24.0% (6/25) receiving placebo ( P = 0.0008). Leronlimab was generally well tolerated with no drug-related serious adverse events reported. Overall, 175 adverse events were reported by 34/52 participants, with 120 (68.6%) adv...