EBioMedicine (Feb 2021)
Pharmacokinetics and predicted neutralisation coverage of VRC01 in HIV-uninfected participants of the Antibody Mediated Prevention (AMP) trials
- Yunda Huang,
- Logashvari Naidoo,
- Lily Zhang,
- Lindsay N. Carpp,
- Erika Rudnicki,
- April Randhawa,
- Pedro Gonzales,
- Adrian McDermott,
- Julie Ledgerwood,
- Margarita M.Gomez Lorenzo,
- David Burns,
- Allan DeCamp,
- Michal Juraska,
- John Mascola,
- Srilatha Edupuganti,
- Nyaradzo Mgodi,
- Myron Cohen,
- Lawrence Corey,
- Philip Andrew,
- Shelly Karuna,
- Peter B. Gilbert,
- Kathryn Mngadi,
- Erica Lazarus
Affiliations
- Yunda Huang
- Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America; Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America; Department of Global Health, University of Washington, Seattle, WA, United States of America; Corresponding author.
- Logashvari Naidoo
- HIV Prevention Research Unit, South African Medical Research Council, Durban, South Africa
- Lily Zhang
- Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America
- Lindsay N. Carpp
- Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America
- Erika Rudnicki
- Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America
- April Randhawa
- Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America
- Pedro Gonzales
- Asociacion Civil Impacta Salud y Educacion, Lima, Perú
- Adrian McDermott
- Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States of America
- Julie Ledgerwood
- Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States of America
- Margarita M.Gomez Lorenzo
- Division of AIDS, National Institute of Allergy and Infectious Diseases, Bethesda, MD, United States of America
- David Burns
- Division of AIDS, National Institute of Allergy and Infectious Diseases, Bethesda, MD, United States of America
- Allan DeCamp
- Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America; Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America
- Michal Juraska
- Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America; Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America
- John Mascola
- Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States of America
- Srilatha Edupuganti
- Division of Infectious Diseases, Department of Medicine, Emory University, Decatur, United States of America
- Nyaradzo Mgodi
- Clinical Trials Research Centre, University of Zimbabwe College of Health Sciences, Harare, Zimbabwe
- Myron Cohen
- Department of Medicine, Division of Infectious Diseases, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599, United States of America; Institute for Global Health and Infectious Diseases, University of North Carolina, Chapel Hill, NC, United States of America
- Lawrence Corey
- Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America; Departments of Medicine and Laboratory Medicine, University of Washington, Seattle, WA, United States of America
- Philip Andrew
- Family Health International, Durham, NC, United States of America
- Shelly Karuna
- Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America
- Peter B. Gilbert
- Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America; Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America; Department of Biostatistics, University of Washington, Seattle, WA, United States of America
- Kathryn Mngadi
- Centre for the AIDS Programme of Research in South Africa, Durban, South Africa
- Erica Lazarus
- Perinatal HIV Research Unit (PHRU), Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, Gauteng, South Africa
- Journal volume & issue
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Vol. 64
p. 103203
Abstract
The phase 2b AMP trials are testing whether the broadly neutralising antibody VRC01 prevents HIV-1 infection in two cohorts: women in sub-Saharan Africa, and men and transgender persons who have sex with men (MSM/TG) in the Americas and Switzerland. We used nonlinear mixed effects modelling of longitudinal serum VRC01 concentrations to characterise pharmacokinetics and predict HIV-1 neutralisation coverage. We found that body weight significantly influenced clearance, and that the mean peripheral volume of distribution, steady state volume of distribution, elimination half-life, and accumulation ratio were significantly higher in MSM/TG than in women. Neutralisation coverage was predicted to be higher in the first (versus second) half of a given 8-week infusion interval, and appeared to be higher in MSM/TG than in women overall. Study cohort differences in pharmacokinetics and neutralisation coverage provide insights for interpreting the AMP results and for investigating how VRC01 concentration and neutralisation correlate with HIV incidence.
