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

Journal of acquired immune deficiency syndromes (1999) 2022 Mar 01

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This study evaluated atazanavir and cobicistat pharmacokinetics during pregnancy compared with postpartum and in infant washout samples. A nonrandomized, open-label, parallel-group, multicenter prospective study of atazanavir and cobicistat pharmacokinetics in pregnant women with HIV and their children. 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. 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. Standard atazanavir/cobicistat dosing during pregnancy results in lower exposure which may increase the risk of virologic failure and perinatal transmission. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

Citation

Jeremiah D Momper, Jiajia Wang, Alice Stek, David E Shapiro, Kathleen M Powis, Mary E Paul, Martina L Badell, Renee Browning, Nahida Chakhtoura, Kayla Denson, Kittipong Rungruengthanakit, Kathleen George, Edmund V Capparelli, Mark Mirochnick, Brookie M Best, IMPAACT P1026s Protocol Team. Pharmacokinetics of Atazanavir Boosted With Cobicistat in Pregnant and Postpartum Women With HIV. Journal of acquired immune deficiency syndromes (1999). 2022 Mar 01;89(3):303-309