Elvitegravir/cobicistat pharmacokinetics in pregnant and postpartum women with HIV

• Type of Material: Article
• Authors: Jeremiah D. Momper, University of California San Diego; Brookie M. Best, University of California San Diego; Jiajia Wang, Harvard T.H. Chan School of Public Health; Edmund V. Capparelli, University of California San Diego; Alice Stek, University of Southern California; Emily Barr, University of Colorado; Martina Badell, Emory University; Edward P. Acosta, University of Alabama Birmingham; Murli Purswani, Icahn School of Medicine at Mount Sinai; Elizabeth Smith, NIAID, Bethesda; Nahida Chakhtoura, NICHD, Bethesda; Kyunghun Park, University of California San Diego; Sandra Burchett, Children's Hospital Boston; David E. Shapiro, Harvard T.H. Chan School of Public Health; Mark Mirochnick, Boston University
• Language: English
• Date: 2018-11-13
• Publisher: Lippincott, Williams & Wilkins
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: Copyright © 2018, Copyright © 2018 Wolters Kluwer Health, Inc.
• Final Published Version (URL): http://dx.doi.org/10.1097/QAD.0000000000001992
• Title of Journal or Parent Work: AIDS
• ISSN: 0269-9370
• Volume: 32
• Issue: 17
• Start Page: 2507
• End Page: 2516
• Grant/Funding Information: Overall support for the International Maternal Pediatric Adolescent AIDS Clinical Trials Network (IMPAACT) was provided by the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH) under Award Numbers UM1AI068632 (IMPAACT LOC), UM1AI068616 (IMPAACT SDMC) and UM1AI106716 (IMPAACT LC), with co-funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and the National Institute of Mental Health (NIMH).; Additional support was provided by Gilead Sciences, Inc.
• Keywords: elvitegravir; Immunology; cobicistat; HIV infection; Infectious Diseases; Life Sciences & Biomedicine; integrase inhibitor; EXPRESSION; Virology; COBICISTAT; Science & Technology; pharmacokinetics; perinatal transmission; pregnancy
• Research Categories: Health Sciences, Public Health; Health Sciences, Pharmacology; Biology, Virology

Abstract

OBJECTIVE: To evaluate elvitegravir and cobicistat pharmacokinetics during pregnancy compared with postpartum and in infant washout samples after delivery. DESIGN: Nonrandomized, open-label, parallel-group, multicenter phase-IV prospective study of antiretroviral pharmacokinetics in HIV-infected pregnant women and their children in the United States. METHODS: Intensive steady-state 24-h pharmacokinetic profiles after 150 mg of elvitegravir and 150 mg of cobicistat given orally in fixed dose combination once-daily were performed during the second trimester, third trimester, and postpartum. Infant washout samples were collected after birth. Elvitegravir and cobicistat were measured in plasma by a validated liquid chromatography with tandem mass spectrometry assay with a lower quantitation limit of 10 ng/ml. A two-tailed Wilcoxon signed-rank test (α = 0.10) was employed for paired within-participant comparisons. RESULTS: Thirty pregnant women taking elvitegravir and cobicistat once-daily enrolled in the study. Compared with paired postpartum data, elvitegravir AUC0-24 was 24% lower in the second trimester [n = 14, P = 0.058, geometric mean ratios (GMR) = 0.76, 90% confidence interval (CI) 0.57-1.0] and 44% lower in the third trimester (n = 24, P = 0.0001, GMR = 0.56, 90% CI 0.42-0.73), while cobicistat AUC0-24 was 44% lower in the second trimester (n = 14, P = 0.0085, GMR = 0.56, 90% CI 0.37-0.85) and 59% lower in the third trimester (n = 24, P < 0.0001, GMR = 0.41, 90% CI 0.30-0.57). Median cord blood elvitegravir concentration was 540.6 ng/ml and the median ratio of cord blood to maternal plasma elvitegravir concentrations was 0.91. CONCLUSION: Standard elvitegravir and cobicistat dosing during pregnancy results in significantly lower exposure which may increase the risk of virologic failure and mother-to-child transmission. Additional studies are needed to optimize elvitegravir and cobicistat dosing regimens in pregnant women.