Kristina M Brooks1, Jeremiah D Momper2, Mauricio Pinilla3, Alice M Stek4, Emily Barr5, Adriana Weinberg6, Jaime G Deville7, Irma L Febo8, Mikhaela Cielo9, Kathleen George10, Kayla Denson11, Kittipong Rungruengthanakit12, David E Shapiro3, Elizabeth Smith13, Nahida Chakhtoura14, James F Rooney15, Richard Haubrich15, Rowena Espina2, Edmund V Capparelli2,16, Mark Mirochnick17, Brookie M Best2,16. 1. Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, Colorado. 2. Department of Clinical Pharmacy, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, San Diego, California. 3. Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. 4. Department of Obstetrics and Gynecology, University of Southern California School of Medicine, Los Angeles, California. 5. Department of Pediatrics. 6. Departments of Pediatrics, Medicine and Pathology, University of Colorado Anschutz Medical Campus, Aurora, Colorado. 7. Division of Infectious Diseases, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California. 8. Department of Pediatrics, School of Medicine, University of Puerto Rico, San Juan, Puerto Rico. 9. Department of Pediatrics, University of Southern California School of Medicine, Los Angeles, California. 10. Family Health International, Durham, North Carolina. 11. Frontier Science & Technology Research Foundation, Inc., Amherst, New York, USA. 12. Research Institute for Health Sciences, Chiang Mai University, Chiang Mai, Thailand. 13. National Institute of Allergy and Infectious Diseases. 14. Maternal and Pediatric Infectious Disease Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Bethesda, Maryland. 15. Gilead Sciences, Inc., Foster City. 16. Pediatrics Department, University of California San Diego - Rady Children's Hospital San Diego, San Diego, California. 17. Division of Neonatology, Boston University School of Medicine, Boston, Massachusetts, USA.
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.
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.
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