Feasibility and Successful Enrollment in a Proof-of-Concept HIV Prevention Trial of VRC01, a Broadly Neutralizing HIV-1 Monoclonal Antibody
Year: 2021
Type: article
Study design: Clinical Trial
Abstract: BACKGROUND: The Antibody-Mediated Prevention trials (HVTN 704/HPTN 085 and HVTN 703/HPTN 081) are the first efficacy trials to evaluate whether VRC01, a broadly neutralizing monoclonal antibody targeting the CD4-binding site of the HIV envelope protein, prevents sexual transmission of HIV-1. HVTN 704/HPTN 085 enrolled 2701 cisgender men and transgender (TG) individuals who have sex with men at 26 sites in Brazil, Peru, Switzerland, and the United States. METHODS: Participants were recruited and retained through early, extensive community engagement. Eligible participants were randomized 1:1:1 to 10 mg/kg or 30 mg/kg of VRC01 or saline placebo. Visits occurred monthly, with intravenous (IV) infusions every 8 weeks over 2 years, for a total of 10 infusions. Participants were followed for 104 weeks after first infusion. RESULTS: The median HVTN 704/HPTN 085 participant age was 28 years; 99% were assigned male sex; 90% identified as cisgender men, 5% as TG women and the remaining as other genders. Thirty-two percent were White, 15% Black, and 57% Hispanic/Latinx. Twenty-eight percent had a sexually transmitted infection at enrollment. More than 23,000 infusions were administered with no serious IV administration complications. Overall, retention and adherence to the study schedule exceeded 90%, and the dropout rate was below 10% annually (7.3 per 100 person-years) through week 80, the last visit for the primary end point. CONCLUSIONS: HVTN 704/HPTN 085 exceeded accrual and retention expectations. With exceptional safety of IV administration and operational feasibility, it paves the way for future large-scale monoclonal antibody trials for HIV prevention and/or treatment.
Authors: Srilatha Edupuganti, Nyaradzo Mgodi, Shelly T. Karuna, Philip Andrew, Erika Rudnicki, Nidhi Kochar, Allan deCamp, Robert De La Grecca, Maija Anderson, Carissa Karg, India Tindale, Elizabeth Greene, Gail B. Broder, Jonathan Lucas, John Hural, Jorge A. Gallardo-Cartagena, Pedro Gonzales, Ian Frank, Magdalena Sobieszczyk, Margarita M. Gomez Lorenzo, David Burns, Peter L. Anderson, Maurine D. Miner, Julie Ledgerwood, John R. Mascola, Peter B. Gilbert, Myron S. Cohen, Lawrence Corey, the HVTN 704/HPTN 085 study group
Institutions: Emory University, University of Zimbabwe, Fred Hutch Cancer Center, University of North Carolina at Chapel Hill, National University of San Marcos, Hospital Nacional Dos de Mayo, University of Pennsylvania, Columbia University Irving Medical Center, Columbia University, National Institutes of Health, National Institute of Allergy and Infectious Diseases, University of Colorado Anschutz, Vaccine Research Center, University of Washington
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: HVTN Laboratory Program, HIV Prevention trials Network (HPTN) Coordinating and Operations Center, Leadership for HIV/AIDS Clinical Trials Networks; HIV Vaccine Trials Network, Leadership Group for a Global HIV Vaccine Clinical Trials Network, HIV Vaccine Trials Network Laboratory Center, HIV Prevention Trials Network Leadership and Operations Center, University of Pennsylvania HIV Clinical Trials Unit, HIV Vaccines Clinical Trials Network Leadership and Operations Center, SDMC: HIV Vaccine Trials Network, Penn Center for AIDS Research, The University of North Carolina Center for AIDS Research, Columbia Collaborative HIV/AIDS Clinical Trials Unit
OpenAlex ID: W3131497256