Srilatha Edupuganti1, Nyaradzo Mgodi2, Shelly T Karuna3, Philip Andrew4, Erika Rudnicki3, Nidhi Kochar3, Allan deCamp3, Robert De La Grecca3, Maija Anderson3, Carissa Karg3, India Tindale3, Elizabeth Greene4, Gail B Broder3, Jonathan Lucas4, John Hural3, Jorge A Gallardo-Cartagena5, Pedro Gonzales6, Ian Frank7, Magdalena Sobieszczyk8, Margarita M Gomez Lorenzo9, David Burns9, Peter L Anderson10, Maurine D Miner3, Julie Ledgerwood11, John R Mascola11, Peter B Gilbert3,12, Myron S Cohen4, Lawrence Corey3. 1. Division of Infectious Disease, Department of Medicine, Emory University, Atlanta, GA. 2. University of Zimbabwe College of Health Sciences Clinical Trials Research Centre, Harare, Zimbabwe. 3. Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA. 4. Institute for Global Health and Infectious Disease, University of North Carolina, Chapel Hill, NC. 5. Centro de Investigaciones Tecnológicas, Biomédicas y Medioambientales, Universidad Nacional Mayor de San Marcos, Lima, Peru. 6. Servicio de Enfermedades Infecciosas y Tropicales, Hospital Nacional Dos de Mayo, Lima. 7. Department of Medicine, Division of Infectious Diseases, University of Pennsylvania, Pennsylvania, PA. 8. Department of Medicine, Division of Infectious Diseases, Columbia University, New York, NY. 9. Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD. 10. Department of Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO. 11. Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD; and. 12. Department of Biostatistics, Univeristy of Washington, Seattle, WA.
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.
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: Yunda Huang; Lily Zhang; Julie Ledgerwood; Nicole Grunenberg; Robert Bailer; Abby Isaacs; Kelly Seaton; Kenneth H Mayer; Edmund Capparelli; Larry Corey; Peter B Gilbert Journal: MAbs Date: 2017-04-03 Impact factor: 5.857
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Authors: Peter B Gilbert; Michal Juraska; Allan C deCamp; Shelly Karuna; Srilatha Edupuganti; Nyaradzo Mgodi; Deborah J Donnell; Carter Bentley; Nirupama Sista; Philip Andrew; Abby Isaacs; Yunda Huang; Lily Zhang; Edmund 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 M Gomez; David N Burns; Julie McElrath; Julie Ledgerwood; Barney S Graham; John R Mascola; Myron Cohen; Lawrence Corey Journal: Stat Commun Infect Dis Date: 2017-06-06
Authors: Simbarashe Takuva; Shelly T Karuna; Michal Juraska; Erika Rudnicki; Srilatha Edupuganti; Maija Anderson; Robert De La Grecca; Martin R Gaudinski; Alice Sehurutshi; Catherine Orrell; Logashvari Naidoo; Javier Valencia; Larissa M Villela; Stephen R Walsh; Philip Andrew; Carissa Karg; April Randhawa; John Hural; Margarita M Gomez Lorenzo; David N Burns; Julie Ledgerwood; John R Mascola; Myron Cohen; Lawrence Corey; Kathy Mngadi; Nyaradzo M Mgodi Journal: J Acquir Immune Defic Syndr Date: 2022-04-01 Impact factor: 3.771
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Authors: Barton F Haynes; Kevin Wiehe; Persephone Borrrow; Kevin O Saunders; Bette Korber; Kshitij Wagh; Andrew J McMichael; Garnett Kelsoe; Beatrice H Hahn; Frederick Alt; George M Shaw Journal: Nat Rev Immunol Date: 2022-08-12 Impact factor: 108.555
Authors: Sarah E Lovelace; Sabrina Helmold Hait; Eun Sung Yang; Madison L Fox; Cuiping Liu; Misook Choe; Xuejun Chen; Elizabeth McCarthy; John-Paul Todd; Ruth A Woodward; Richard A Koup; John R Mascola; Amarendra Pegu Journal: iScience Date: 2022-09-05