Pharmacokinetics of tenofovir alafenamide with and without cobicistat in pregnant and postpartum women living with HIV
| Autor: | Adriana Weinberg, Richard Haubrich, Mikhaela Cielo, Mauricio Pinilla, Kittipong Rungruengthanakit, Alice Stek, Jaime G. Deville, Irma Febo, Impaact P s Protocol Team, Emily Barr, David Shapiro, James F. Rooney, Rowena Espina, Kathleen George, Mark Mirochnick, Nahida Chakhtoura, Edmund V. Capparelli, Brookie M. Best, Kristina M Brooks, Elizabeth Smith, Jeremiah D. Momper, Kayla Denson |
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| Rok vydání: | 2020 |
| Předmět: |
Adult
0301 basic medicine medicine.medical_specialty Anti-HIV Agents Immunology HIV Infections Tenofovir alafenamide Article 03 medical and health sciences 0302 clinical medicine Pharmacokinetics Pregnancy Emtricitabine Humans Immunology and Allergy Medicine Prospective Studies 030212 general & internal medicine Tenofovir Prospective cohort study reproductive and urinary physiology Alanine business.industry Obstetrics Adenine Cobicistat Postpartum Period medicine.disease Confidence interval 030104 developmental biology Infectious Diseases Cord blood Female business Postpartum period |
| Zdroj: | AIDS |
| ISSN: | 1473-5571 0269-9370 |
| DOI: | 10.1097/qad.0000000000002767 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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