Pharmacokinetics of Atazanavir Boosted With Cobicistat in Pregnant and Postpartum Women With HIV.

Autor:	Momper JD; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA., Wang J; Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, MA., Stek A; Keck School of Medicine, University of Southern California, Los Angeles, CA., Shapiro DE; Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, MA., Powis KM; Departments of Internal Medicine and Pediatrics, Massachusetts General Hospital, Boston, MA., Paul ME; Department of Pediatrics, Baylor College of Medicine, Houston, TX., Badell ML; Department of Gynecology & Obstetrics, Emory University School of Medicine, Atlanta, GA., Browning R; National Institute of Allergy and Infectious Diseases, Bethesda, MD., Chakhtoura N; National Institute of Child Health and Human Development, Bethesda, MD., Denson K; Frontier Science & Technology Research Foundation, Inc, Amherst, NY., Rungruengthanakit K; Research Institute for Health Sciences, Chiang Mai University, Chiang Mai, Thailand., George K; Family Health International, Durham, NC; and., Capparelli EV; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA., Mirochnick M; Division of Neonatology, Boston University, Boston, MA., Best BM; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA.
Jazyk:	angličtina
Zdroj:	Journal of acquired immune deficiency syndromes (1999) [J Acquir Immune Defic Syndr] 2022 Mar 01; Vol. 89 (3), pp. 303-309.
DOI:	10.1097/QAI.0000000000002856
Abstrakt:	Background: This study evaluated atazanavir and cobicistat pharmacokinetics during pregnancy compared with postpartum and in infant washout samples. Setting: A nonrandomized, open-label, parallel-group, multicenter prospective study of atazanavir and cobicistat pharmacokinetics in pregnant women with HIV and their children. Methods: Intensive steady-state 24-hour pharmacokinetic profiles were performed after administration of 300 mg of atazanavir and 150 mg of cobicistat orally in fixed-dose combination once daily during the second trimester, third trimester, and postpartum. Infant washout samples were collected after birth. Atazanavir and cobicistat were measured in plasma by validated high-performance liquid chromatography-ultraviolet and liquid chromatography-tandem mass spectrometry assays, respectively. A 2-tailed Wilcoxon signed-rank test (α = 0.10) was used for paired within-participant comparisons. Results: A total of 11 pregnant women enrolled in the study. Compared with paired postpartum data, atazanavir AUC0-24 was 26% lower in the second trimester [n = 5, P = 0.1875, geometric mean of ratio (GMR) = 0.739, 90% CI: 0.527 to 1.035] and 54% lower in the third trimester (n = 6, GMR = 0.459, P = 0.1563, 90% CI: 0.190 to 1.109), whereas cobicistat AUC0-24 was 35% lower in the second trimester (n = 5, P = 0.0625, GMR = 0.650, 90% CI: 0.493 to 0.858) and 52% lower in the third trimester (n = 7, P = 0.0156, GMR = 0.480, 90% CI: 0.299 to 0.772). The median (interquartile range) 24-hour atazanavir trough concentration was 0.21 μg/mL (0.16-0.28) in the second trimester, 0.21 μg/mL (0.11-0.56) in the third trimester, and 0.61 μg/mL (0.42-1.03) in postpartum. Placental transfer of atazanavir and cobicistat was limited. Conclusions: Standard atazanavir/cobicistat dosing during pregnancy results in lower exposure which may increase the risk of virologic failure and perinatal transmission. Competing Interests: The authors have no conflicts of interest to disclose. (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)
Databáze:	MEDLINE
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