Pharmacokinetics of atazanavir boosted with cobicistat in pregnant and postpartum women with HIV.

Background This study evaluated atazanavir and cobicistat pharmacokinetics during pregnancy compared to postpartum and in infant washout samples. Setting A nonrandomized, open-label, parallel-group, multi-center 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 HPLC-UV and 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 11 pregnant women enrolled in the study. Compared to 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 - 1.035) and 54% lower in the third trimester (n=6, GMR=0.459, P=0.1563, 90% CI 0.190 - 1.109), while cobicistat AUC0-24 was 35% lower in the second trimester (n=5, P=0.0625, GMR=0.650, 90% CI 0.493 - 0.858) and 52% lower in the third trimester (n=7, p=0.0156, GMR=0.480, 90% CI 0.299 - 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) 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.