Jeremiah D Momper1, Jiajia Wang2, Alice Stek3, David E Shapiro2, Kathleen M Powis4, Mary E Paul5, Martina L Badell6, Renee Browning7, Nahida Chakhtoura8, Kayla Denson9, Kittipong Rungruengthanakit10, Kathleen George11, Edmund V Capparelli1, Mark Mirochnick12, Brookie M Best1. 1. Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA. 2. Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, MA. 3. Keck School of Medicine, University of Southern California, Los Angeles, CA. 4. Departments of Internal Medicine and Pediatrics, Massachusetts General Hospital, Boston, MA. 5. Department of Pediatrics, Baylor College of Medicine, Houston, TX. 6. Department of Gynecology & Obstetrics, Emory University School of Medicine, Atlanta, GA. 7. National Institute of Allergy and Infectious Diseases, Bethesda, MD. 8. National Institute of Child Health and Human Development, Bethesda, MD. 9. Frontier Science & Technology Research Foundation, Inc, Amherst, NY. 10. Research Institute for Health Sciences, Chiang Mai University, Chiang Mai, Thailand. 11. Family Health International, Durham, NC; and. 12. Division of Neonatology, Boston University, Boston, MA.
Abstract
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.
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.
Authors: Sarita D Boyd; Mario R Sampson; Prabha Viswanathan; Kimberly A Struble; Vikram Arya; Adam I Sherwat Journal: AIDS Date: 2019-05-01 Impact factor: 4.177
Authors: Alice Stek; Brookie M Best; Jiajia Wang; Edmund V Capparelli; Sandra K Burchett; Regis Kreitchmann; Kittipong Rungruengthanakit; Tim R Cressey; Lynne M Mofenson; Elizabeth Smith; David Shapiro; Mark Mirochnick Journal: J Acquir Immune Defic Syndr Date: 2015-09-01 Impact factor: 3.731
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