Pharmacokinetic interaction assessment of an HIV broadly neutralizing monoclonal antibody VRC07-523LS: a cross-protocol analysis of three phase 1 trials in people without HIV

作者：Tariro Dianah Chawana, Stephen R. Walsh, Lynda Stranix‐Chibanda, Zvavahera M. Chirenje, Chenchen Yu, Lily Zhang, Kelly E. Seaton, Jack Heptinstall, Lu Zhang, Carmen A. Paez, Theresa Gamble, Shelly Karuna, P. Andrew, Brett Hanscom, Magdalena E. Sobieszczyk, Srilatha Edupuganti, Cynthia L. Gay, Sharon Mannheimer, Christopher B. Hurt, Kathryn E. Stephenson, Laura Polakowski, Hans Spiegel, Margaret Yacovone, Stephanie Regenold, Catherine Yen, Jane Baumblatt, Lúcio Gama, Dan H. Barouch, Estelle Piwowar-Manning, Richard A. Koup, Georgia D. Tomaras, Ollivier Hyrien, Alison C. Roxby, Yunda Huang, on behalf of the HVTN 127/HPTN 087, HVTN 130/HPTN 089 and HVTN 136/HPTN 092 Study Teams · 发表于：BMC Immunology · 年份：2025 · DOI：10.1186/s12865-025-00687-7 · 被引用次数：3 · 研究领域：HIV Research and Treatment、Monoclonal and Polyclonal Antibodies Research、HIV/AIDS drug development and treatment

VRC07-523LS is a safe and well-tolerated monoclonal antibody (mAb) targeting the CD4 binding site on the HIV envelope (Env) trimer. Efficacy of VRC07-523LS, in combination with mAbs targeting other HIV epitopes, will be evaluated in upcoming trials to prevent HIV acquisition in adults. However, differences in the pharmacokinetics (PK) of VRC07-523LS when administered alone vs. in combination with other mAbs have not been formally assessed. We performed a cross-protocol analysis of three clinical trials and included data from a total of 146 adults without HIV who received intravenous (n = 95) or subcutaneous (n = 51) VRC07-523LS, either alone ('single'; n = 100) or in combination with 1 or 2 other mAbs ('combined'; n = 46). We used an open, two-compartment population PK model to describe serum concentrations of VRC07-523LS over time, accounting for inter-individual variabilities. We compared individual-level PK parameters between the combined vs. single groups using the targeted maximum likelihood estimation method to adjust for participant characteristics. No significant differences were observed in clearance rate, inter-compartmental clearance, distribution half-life, or total VRC07-523LS exposure over time. However, for the combined group, mean central volume of distribution, peripheral volume of distribution, and elimination half-life were slightly greater, corresponding to slightly lower predicted concentrations early post-administration with high levels being maintained ...