Safety, Tolerability, and Pharmacokinetics of the Broadly Neutralizing Human Immunodeficiency Virus (HIV)-1 Monoclonal Antibody VRC01 in HIV-Exposed Newborn Infants
Year: 2019
Type: article
Study design: Clinical Trial
Abstract: BACKGROUND: Although mother-to-child human immunodeficiency virus (HIV) transmission has dramatically decreased with maternal antiretroviral therapy, breast milk transmission accounts for most of the 180 000 new infant HIV infections annually. Broadly neutralizing antibodies (bNAb) may further reduce transmission. METHODS: A Phase 1 safety and pharmacokinetic study was conducted: a single subcutaneous (SC) dose of 20 or 40 mg/kg (Dose Groups 1 and 2, respectively) of the bNAb VRC01 was administered to HIV-exposed infants soon after birth. Breastfeeding infants (Dose Group 3) received 40 mg/kg SC VRC01 after birth and then 20 mg/kg/dose SC monthly. All infants received appropriate antiretroviral prophylaxis. RESULTS: Forty infants were enrolled (21 in the United States, 19 in Africa). Subcutaneous VRC01 was safe and well tolerated with only mild-to-moderate local reactions, primarily erythema, which rapidly resolved. For multiple-dose infants, local reactions decreased with subsequent injections. VRC01 was rapidly absorbed after administration, with peak concentrations 1-6 days postdose. The 40 mg/kg dose resulted in 13 of 14 infants achieving the serum 50 micrograms (mcg)/mL target at day 28. Dose Group 3 infants maintained concentrations greater than 50 mcg/mL throughout breastfeeding. CONCLUSIONS: Subcutaneous VRC01 as single or multiple doses is safe and well tolerated in very young infants and is suitable for further study to prevent HIV transmission in infants.
Authors: Coleen K Cunningham, Elizabeth J McFarland, R Leavitt Morrison, Edmund V Capparelli, Jeffrey T Safrit, Lynne M Mofenson, Bonnie Mathieson, Megan E Valentine, Charlotte Perlowski, Betsy Smith, Rohan Hazra, Lynette Purdue, Petronella Muresan, Paul A Harding, Tapiwa Mbengeranwa, Lisa-Gaye Robinson, Andrew Wiznia, Gerhard Theron, Bob Lin, Robert T Bailer, John R Mascola, Barney S Graham, IMPAACT P1112 team, Grace Aldrovandi, Frederic Bone, Dale Dayton, Benjamin Johnston, Patricia Morgan, Kathryn Myers, Nicole Tobin, Bonnie Zimmer, Magdel Rossouw, Lindie Rossouw, Jeanne Louw, Joanna Dobroszycki, Marlene Burey, Raphaelle Auguste, Kathleen K Graham, Hanna Major-Wilson, Tsungai Mhembere, Sukunena Maturure, Mutsa Bwakura-Dangarembizi, Emily Barr, Jennifer Dunn, Carrie Glenny, Carrie Chambers, Mahboobullah Mirza Baig, Murli Purswani, Jaime G Deville, Karin Nielsen-Saines, Christina Shin, Michele F Carter, Ann Chahroudi, Alexis Ahonen, Martina Badell, Rana Chakraborty, Allison Agwu, W Christopher Golden, Thuy Anderson, Aleisha Collinson-Streng, Rodrigo Diaz-Velasco, Nicolas Rosario, Elvia Pérez, Wanda I Marrero, Irma Febo, Ruth Santos, Carmen D Zorrilla
Institutions: Duke University, University of Colorado Anschutz, Harvard University, University of California San Diego, Elizabeth Glaser Pediatric AIDS Foundation, National Institutes of Health, Office of AIDS Research, Family Health International 360, National Institute of Allergy and Infectious Diseases, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Frontier Science & Technology Research Foundation, Inc., University of Zimbabwe, Children's Diagnostic & Treatment Center, Broward Health, Albert Einstein College of Medicine, Jacobi Medical Center, Stellenbosch University, Vaccine Research Center
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: National Institutes of Health, Center for AIDS Research, Duke University, National Institute of Mental Health, National Institute of Allergy and Infectious Diseases, National Institute of Child Health and Human Development, National Center for Advancing Translational Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development
OpenAlex ID: W2984342233