Elvitegravir/cobicistat pharmacokinetics in pregnant and postpartum women with HIV

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 anti retroviral 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 (alpha= 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 AUC(0-24) 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 AUC(0-24) was 44% lower in the second trimester (n = 14, P = 0.0085, GMR = 0.56, 90% CI 0.3 7-0.85) 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. Copyright (C) 2018 Wolters Kluwer Health, Inc. All rights reserved.