Pharmacokinetics of tenofovir alafenamide with and without cobicistat in pregnant and postpartum women living with HIV

Abstract

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 cord blood samples were collected at delivery, and washout pharmacokinetic samples were collected in infants. TAF concentrations were quantified using liquid chromatography/mass spectrometry. 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 with postpartum, but comparable with those measured in nonpregnant adults. TAF was below the lower limit of quantitation in 43 of 44 cord blood, 41 of 45 maternal blood at delivery, and all infant washout samples.

Conclusion: TAF exposures were comparable or higher than those measured in nonpregnant 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.

Conflict of interest statement

Conflicts of Interest: JDM receives research funding (paid to his institution) from Gilead Sciences, Inc.. AW receives research funding (paid to her institution) from Merck & Co. and GlaxoSmithKline. JFR and RH are employees of Gilead Sciences, Inc., and hold stock interests in the company. MM receives research funding (paid to his institution) from Gilead Sciences, Inc., Merck & Co., and ViiV Healthcare. The remaining authors have none to declare.

Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Figures

Figure 1.

Median (IQR) concentration-time curves during the 2nd trimester, 3rd trimester, and postpartum for (a) TAF 10 mg with cobicistat and (b) TAF 25 mg (without boosting). Dotted lines indicate 50th percentile concentrations measured in non-pregnant adults.

Figure 2.

Median (IQR) TAF exposures during the 2nd trimester, 3rd trimester, and postpartum for (a) TAF 10 mg with cobicistat and (b) TAF 25 mg (unboosted). Gray shading indicates 10th and 90th percentile exposures from phase II/III studies in non-pregnant adults, and the dashed line indicates the threshold for real-time comparisons. In the TAF 10 mg with cobicistat arm, there was one woman during the second trimester and a second woman during the third trimester and postpartum with drug concentrations below the LLOQ at all time points (not included). The summary tables below each figure reflect number (N) (percentage [%]) of women exceeding the AUC target for real-time comparisons (132 ng*h/mL) and phase 3 data (88 ng*h/mL).