Safety, Tolerability, and Pharmacokinetics of the Broadly Neutralizing Human Immunodeficiency Virus (HIV)-1 Monoclonal Antibody VRC01 in HIV-Exposed Newborn Infants.

Autor:	Cunningham CK; Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina, USA., McFarland EJ; Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA., Morrison RL; Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA., Capparelli EV; University of California, San Diego, California, USA., Safrit JT; Elizabeth Glaser Pediatric AIDS Foundation, Washington District of Columbia, USA., Mofenson LM; Elizabeth Glaser Pediatric AIDS Foundation, Washington District of Columbia, USA., Mathieson B; Formerly at National Institutes of Health Office of AIDS Research, National Institutes of Health, Bethesda, Maryland, USA., Valentine ME; FHI 360, Durham, North Carolina, USA., Perlowski C; FHI 360, Durham, North Carolina, USA., Smith B; Division of AIDS, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA., Hazra R; Maternal and Pediatric Infectious Disease Branch Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland, USA., Purdue L; National Institute of Allergy and Infectious Diseases, Division of AIDS (Contractor), Bethesda, Maryland, USA., Muresan P; Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.; Frontier Science Foundation, Brookline, Massachusetts, USA., Harding PA; Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA., Mbengeranwa T; University of Zimbabwe College of Health Sciences-Clinical Trials Research Centre, Harare, Zimbabwe., Robinson LG; Children's Diagnostic and Treatment Center, Broward Health, Fort Lauderdale, Florida, USA., Wiznia A; Jacobi Medical Center, Department of Pediatrics, Albert Einstein College of Medicine, Bronx, New York, USA., Theron G; Department of Obstetrics and Gynaecology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa., Lin B; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA., Bailer RT; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA., Mascola JR; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA., Graham BS; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Jazyk:	angličtina
Zdroj:	The Journal of infectious diseases [J Infect Dis] 2020 Jul 23; Vol. 222 (4), pp. 628-636.
DOI:	10.1093/infdis/jiz532
Abstrakt:	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. (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
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