Pharmacokinetics of tenofovir alafenamide with and without cobicistat in pregnant and postpartum women living with HIV: Results from IMPAACT P1026s.

OBJECTIVE To evaluate the pharmacokinetics of tenofovir alafenamide (TAF) 10 mg with cobicistat and 25 mg without boosting in pregnant and postpartum women with HIV and to characterize TAF placental transfer and infant washout pharmacokinetics. DESIGN Open-label, multicenter phase IV prospective study of TAF pharmacokinetics during pregnancy, postpartum, delivery and infant washout. METHODS Pregnant women receiving TAF 10 mg with cobicistat or TAF 25 mg without boosting as part of clinical care had intensive pharmacokinetic assessments performed during the second and third trimesters, and 6-12 weeks postpartum. Maternal and infant blood samples were collected at delivery, and washout pharmacokinetic samples were collected in infants. TAF concentrations were quantified using LC/MS. Comparisons between pregnancy and postpartum were made using geometric mean ratios (90% confidence intervals) and Wilcoxon signed-rank tests. RESULTS Thirty-one pregnant women receiving TAF 10 mg with cobicistat-boosting and 27 women receiving TAF 25 mg without boosting were enrolled. TAF exposures did not significantly differ between pregnancy and postpartum when administered as 10 mg with cobicistat. Antepartum TAF exposures with the 25 mg dose were 33-43% lower in comparison to postpartum, but comparable to those measured in non-pregnant adults. TAF was below the lower limit of quantitation in 43/44 cord blood, 41/45 maternal blood at delivery, and all infant washout samples. CONCLUSIONS TAF exposures were comparable or higher than those measured in non-pregnant adults during pregnancy and postpartum. These findings provide reassurance on adequate TAF exposures during pregnancy, and support efforts to expand the use of TAF in pregnant women with HIV.