Safety and Pharmacokinetics of Intravenous 10-1074 and VRC01LS in Young Children.

Autor:	Capparelli EV; Department of Pediatrics, University of California, San Diego, La Jolla, CA., Ajibola G; Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana., Maswabi K; Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana., Holme MP; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA., Bennett K; Bennett Statistical Consulting Inc, Ballston Lake, NY., Powis KM; Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA.; Departments of Internal Medicine and Pediatrics, Massachusetts General Hospital, Boston, MA., Moyo S; Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana., Mohammed T; Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana., Maphorisa C; Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana., Hughes MD; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA., Seaton KE; Center for Human Systems Immunology, Duke University School of Medicine, Department of Surgery, Durham, NC., Tomaras GD; Center for Human Systems Immunology, Duke University School of Medicine, Department of Surgery, Durham, NC., Mosher S; Center for Human Systems Immunology, Duke University School of Medicine, Department of Surgery, Durham, NC., Taylor A; Vaccine Research Center, Bethesda, MD., O'Connell S; Vaccine Research Center, Bethesda, MD., Narpala S; Vaccine Research Center, Bethesda, MD., Mcdermott A; Vaccine Research Center, Bethesda, MD., Caskey M; Laboratory of Molecular Immunology, Rockefeller University, New York, NY., Gama L; Vaccine Research Center, Bethesda, MD., Lockman S; Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA.; Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA., Jean-Philippe P; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD., Makhema J; Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA., Kuritzkes DR; Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA.; Harvard Medical School, Boston, MA; and., Lichterfeld M; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA., Shapiro RL; Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA.
Jazyk:	angličtina
Zdroj:	Journal of acquired immune deficiency syndromes (1999) [J Acquir Immune Defic Syndr] 2022 Oct 01; Vol. 91 (2), pp. 182-188.
DOI:	10.1097/QAI.0000000000003033
Abstrakt:	Background: Broadly neutralizing monoclonal antibodies (bNAbs) suppress HIV-1 RNA and may deplete residual viral reservoirs. We evaluated the safety and pharmacokinetics (PK) of dual intravenous VRC01LS and 10-1074 in very early-treated children with HIV-1 on suppressive antiretroviral treatment (ART). Setting: Botswana. Methods: Children with HIV-1 (median age 3.1 years) on ART from <7 days old were enrolled. In phase A, 6 children received 10-1074 (30 mg/kg at day 0, 28, and 56) and 6 children received VRC01LS (30 mg/kg at day 0, 10 mg/kg at days 28 and 56) by intravenous infusion. In phase B, 6 children received the 2 bNAbs combined (with higher VRC01LS maintenance dose, 15 mg/kg) every 4 weeks for 32 weeks with PK evaluations over 8 weeks. Population PK models were developed to predict steady-state concentrations. Results: BNAb infusions were well tolerated. There were no infusion reactions nor any bNAb-related grade 3 or 4 events. The median (range) first dose Cmax and trough (day 28) combined from both phases were 1405 (876-1999) μg/mL and 133 (84-319) μg/mL for 10-1074 and 776 (559-846) μg/mL and 230 (158-294) μg/mL for VRC01LS. No large differences in bNAb clearances were observed when given in combination. The estimated VRC01LS half-life was shorter than in adults. Predicted steady-state troughs [median (90% prediction interval)] were 261 (95-565) and 266 (191-366) μg/mL for 10-1074 and VRC01LS, respectively, when given in combination. Conclusions: 10-1074 and VRC01LS were safe and well-tolerated among children receiving ART. Troughs exceeded minimal targets with every 4-week administration of 10-1074 at 30 mg/kg and VRC01LS at 15 mg/kg. Competing Interests: The authors have no conflicts of interest to disclose. (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)
Databáze:	MEDLINE
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