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 antiretroviral pharmacokinetics in HIV-infected pregnant women and their children in the United States. Methods: Intensive steady-state 24-h pharmacokinetic profiles after 150mg of elvitegravir and 150mg 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 (a 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, P0.0001, 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.