Safety and antiviral effect of a triple combination of HIV-1 broadly neutralizing antibodies: a phase 1/2a trial

作者：Boris Jülg, Victoria E. Walker-Sperling, Kshitij Wagh, Malika Aïd, Kathryn E. Stephenson, Rebecca Zash, Jinyan Liu, Joseph P. Nkolola, Amelia Hoyt, Mike Castro, Leonid Serebryannyy, Katherine E. Yanosick, Tessa Speidel, Erica N. Borducchi, Tetyana Murzda, Lori F. Maxfield, Roberto C. Arduino, Adrian B. McDermott, Lúcio Gama, Elena E. Giorgi, Richard A. Koup, Michael S. Seaman, Charlotte-Paige Rolle, Edwin DeJesus, Wenjun Li, Bette Korber, Dan H. Barouch · 发表于：Nature Medicine · 年份：2024 · DOI：10.1038/s41591-024-03247-5 · 被引用次数：60 · 研究领域：HIV Research and Treatment、Herpesvirus Infections and Treatments、Hepatitis C virus research

Human immunodeficiency virus type 1 (HIV-1)-specific broadly neutralizing monoclonal antibodies (bNAbs) have to date shown transient viral suppression when administered as monotherapy or as a cocktail of two antibodies1–4. A combination of three bNAbs provides improved neutralization coverage of global viruses, which may more potently suppress viral escape and rebound5–7. Here we performed an open-label, two-part study evaluating a single intravenous dose of HIV-1 bNAbs, PGT121, PGDM1400 and VRC07-523LS, in six adults without HIV in part 1 and a multicenter trial of up to six monthly infusions of these three bNAbs in 12 people living with HIV with an antiretroviral therapy (ART) interruption in part 2. The primary endpoints were safety, tolerability and pharmacokinetics, and the secondary endpoints in part 2 were antiviral activity following ART discontinuation, changes in CD4+ T cell counts and development of HIV-1 sequence mutations associated with bNAb resistance. The trial met its prespecified endpoints. The bNAb treatment was generally safe and well tolerated. In part 2, 83% of participants (10 of 12) maintained virologic suppression for the duration of antibody therapy for at least 28 weeks, and 42% of participants (5 of 12) showed virologic suppression for at least 38–44 weeks, despite the decline of serum bNAb concentrations to low or undetectable levels. In exploratory analyses, early viral rebound in two individuals correlated with baseline resistance to PGT121 and ...