Pharmacokinetics of darunavir and cobicistat in pregnant and postpartum women with HIV

Objective: To evaluate darunavir 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 darunavir and cobicistat pharmacokinetics in pregnant women with HIV and their children in the United States. Methods: Intensive steady-state 24-h pharmacokinetic profiles were performed after administration of 800 mg of darunavir 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. Darunavir and cobicistat were measured in plasma by validated HPLC-UV and liquid chromatography with tandem mass spectrometry detection (LC-MS)/MS assays, respectively. A two-tailed Wilcoxon signed-rank test (α = 0.10) was employed for paired within-participant comparisons. Results: A total of 29 pregnant women receiving darunavir and cobicistat once-daily enrolled in the study. Compared with paired postpartum data, darunavir AUC0--24 was 53% lower in the second trimester [n = 12, P = 0.0024, geometric mean of ratio (GMR)=0.47, 90% confidence interval (CI) 0.33 – 0.68] and 56% lower in the third trimester (n = 18, P 
Source: AIDS - Category: Infectious Diseases Tags: CLINICAL SCIENCE Source Type: research