Basis and Statistical Design of the Passive HIV-1 Antibody Mediated Prevention (AMP) Test-of-Concept Efficacy Trials

作者：Peter B. Gilbert, Michal Juraska, Allan C. deCamp, Shelly Karuna, Srilatha Edupuganti, Nyaradzo Mgodi, Deborah Donnell, Carter Bentley, Nirupama Sista, P. Andrew, Abby Isaacs, Yunda Huang, Lily Zhang, Edmund V. Capparelli, Nidhi Kochar, Jing Wang, Susan H. Eshleman, Kenneth H. Mayer, Craig A. Magaret, John Hural, James G. Kublin, Glenda Gray, David C. Montefiori, Margarita Gomez, David Burns, Julie McElrath, Julie E. Ledgerwood, Barney S. Graham, John R. Mascola, Myron S. Cohen, Lawrence Corey · 发表于：Statistical Communications in Infectious Diseases · 年份：2017 · DOI：10.1515/scid-2016-0001 · 被引用次数：96 · 研究领域：HIV Research and Treatment、HIV/AIDS drug development and treatment、Biological Research and Disease Studies

BACKGROUND: Anti-HIV-1 broadly neutralizing antibodies (bnAbs) have been developed as potential agents for prevention of HIV-1 infection. The HIV Vaccine Trials Network and the HIV Prevention Trials Network are conducting the Antibody Mediated Prevention (AMP) trials to assess whether, and how, intravenous infusion of the anti-CD4 binding site bnAb, VRC01, prevents HIV-1 infection. These are the first test-of-concept studies to assess HIV-1 bnAb prevention efficacy in humans. METHODS: The AMP trials are two parallel phase 2b HIV-1 prevention efficacy trials conducted in two cohorts: 2700 HIV-uninfected men and transgender persons who have sex with men in the United States, Peru, Brazil, and Switzerland; and 1500 HIV-uninfected sexually active women in seven countries in sub-Saharan Africa. Participants are randomized 1:1:1 to receive an intravenous infusion of 10 mg/kg VRC01, 30 mg/kg VRC01, or a control preparation every 8 weeks for a total of 10 infusions. Each trial is designed (1) to assess overall prevention efficacy (PE) pooled over the two VRC01 dose groups vs. control and (2) to assess VRC01 dose and laboratory markers as correlates of protection (CoPs) against overall and genotype- and phenotype-specific infection. RESULTS: Each AMP trial is designed to have 90% power to detect PE > 0% if PE is ≥ 60%. The AMP trials are also designed to identify VRC01 properties (i.e., concentration and effector functions) that correlate with protection and to provide insight into me...