Safety, pharmacokinetics, and neutralisation activity of PGDM1400LS, VRC07-523LS, and PGT121.414.LS infused intravenously or subcutaneously (HVTN 140/HPTN 101 part B): a phase 1, randomised trial

作者：Sharana Mahomed, Sharana Mahomed, Carmen A. Paez, Yunda Huang, Kelly E Seaton, Chenchen Yu, Kevin Gillespie, Maurine D. Miner, Shelly Karuna, Theresa Gamble, Jack Heptinstall, Elize Domin, Haili Tang, Lu Zhang, Fei Gao, Margaret Yacovone, Hans M L Spiegel, Julie Dumond, Maija Anderson, Estelle Piwowar-Manning, Bonnie J. Dye, India Tindale, Lori Proulx-Burns, Meg Trahey, Simbarashe Takuva, Azwidihwi Takalani, Veronique Bailey, Spyros A. Kalams, Hyman Scott, Josphat Kosgei, Sinéad Delany-Moretlwe, Sheetal Kassim, Fatima Laher, Z Mike Chirenje, Yeukai Musodza, Felix Mhlanga, Nonhlanhla Mkhize, Joshua A. Weiner, Margaret E. Ackerman, M Juliana McElrath, Michael Pensiero, Lúcio Gama, Dan H. Barouch, Lawrence Corey, Myron S Cohen, David C. Montefiori, Georgia D. Tomaras, Marc Siegel, Colleen F. Kelley, Margaret E. Ackerman, Maija Anderson, Michael Archibald, Kathryn Axelrod, Veronique Bailey, Saman Baral, Dan H. Barouch, Gail Broder, Wairimu Chege, Shawn Chiambah, Kelvin Chiong, Z. Mike Chirenje, Myron S Cohen, Lawrence Corey, Sinéad Delany-Moretlwe, Elize Domin, Jaiden Dumas, Julie Dumond, Bonnie J. Dye, Lúcio Gama, Theresa Gamble, Fei Gao, Kevin Gillespie, Chelsea Greer, Jen Hanke, Nicholas Hastings, Jack Heptinstall, Nate Holm, Yunda Huang, Zoe Jones, Spyros A. Kalams, DR. GEOFFREY KAMAU, Shelly T. Karuna, Sheetal Kassim, Colleen Kelley, Robert Klitzman, Josphat Kosgei, Gabriela Kovacikova, Fatima Laher, Jonathan Lucas, Jonathan Lucas, Sharana Mahomed, Sharana Mahomed, Anders McConachie, M. Juliana McElrath, Tara McNair, Felix Mhlanga, Maurine D. Miner, Nonhlanhla Mkhize, David C. Montefiori, Amber Moser, Yeukai Musodza, Carmen A. Paez, Michael Pensiero, Estelle Piwowar-Manning, Lori Proulx-Burns, Lynette Purdue, April Randhawa, Laurie Rinn, Sheetal Sawant, Hyman Scott, Kelly Seaton, Angelina Sharak, Marc Siegel, Hans M.L. Spiegel, Kenneth R. Stroop, Shonda E. Sumner, Azwidihwi Takalani, Simbarashe Takuva, Haili Tang, India Tindale, Georgia D. Tomaras, M.D Turner, Lenka Tswenyana, M.D Turner, Joshua A. Weiner, Haven Wilvich, Margaret Yacovone, Nicole Yates, Hannah Yellin, Ntando Yola, Chenchen Yu, Lu Zhang · 发表于：The Lancet HIV · 年份：2026 · DOI：10.1016/s2352-3018(25)00356-x · 研究领域：HIV Research and Treatment、HIV/AIDS drug development and treatment、Renal Transplantation Outcomes and Treatments

BACKGROUND: Passive immunisation with a combination of broadly neutralising monoclonal antibodies (mAbs) presents a potential HIV-1 prevention modality. This study (HVTN 140/HPTN 101) sought to evaluate PGDM1400LS (targeting V3-glycan) administered alone (part A, previously reported), and in combination (part B) with VRC07-523LS (targeting CD4 binding site) and PGT121.414.LS (targeting V2-apex) in healthy adults without HIV-1. METHODS: The study was a phase 1, multicentre, randomised, open-label trial done across the USA (five sites), Kenya (one site), South Africa (four sites), and Zimbabwe (three sites). Part B participants were randomly assigned to five groups (n=16 each), all receiving the three mAbs at months 0 and 4: infusion group T6 (20 mg/kg each mAb intravenously), T7 (20 mg/kg each mAb subcutaneously), T8 (1·4 g each mAb intravenously), T9 (1·4 g each mAb subcutaneously), and T10 (40 mg/kg each mAb intravenously). Primary endpoints were safety and tolerability throughout the study, and pharmacokinetics and neutralising activity on days 0, 3, 6, 28, 56, 112, 168, 224, and 280. Serum mAb concentrations over time were assessed via a validated anti-idiotype binding assay and analysed with two-compartment population pharmacokinetics models. Serum neutralisation titres were assessed by a validated TZM-bl assay. The study is registered at ClinicalTrials.gov (NCT05184452) and is complete. FINDINGS: For the 80 part B participants enrolled from March 21 to Oct 5, 2022, the m...