LAUSR

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.