Dataset Information

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.

SUBMITTER: Brooks KM

PROVIDER: S-EPMC8238253 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Publications

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

Brooks Kristina M KM Momper Jeremiah D JD Pinilla Mauricio M Stek Alice M AM Barr Emily E Weinberg Adriana A Deville Jaime G JG Febo Irma L IL Cielo Mikhaela M George Kathleen K Denson Kayla K Rungruengthanakit Kittipong K Shapiro David E DE Smith Elizabeth E Chakhtoura Nahida N Rooney James F JF Haubrich Richard R Espina Rowena R Capparelli Edmund V EV Mirochnick Mark M Best Brookie M BM

AIDS (London, England) 20210301 3

<h4>Objective</h4>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.<h4>Design</h4>Open-label, multicenter phase IV prospective study of TAF pharmacokinetics during pregnancy, postpartum, delivery, and infant washout.<h4>Methods</h4>Pregnant women receiving TAF 10 mg with cobicistat or TAF 25 mg without boosting as ...[more]

PMID: 33252495

Similar Datasets

Project description:ObjectiveTo evaluate elvitegravir and cobicistat pharmacokinetics during pregnancy compared with postpartum and in infant washout samples after delivery.DesignNonrandomized, open-label, parallel-group, multicenter phase-IV prospective study of antiretroviral pharmacokinetics in HIV-infected pregnant women and their children in the United States.MethodsIntensive steady-state 24-h pharmacokinetic profiles after 150 mg of elvitegravir and 150 mg of cobicistat given orally in fixed dose combination once-daily were performed during the second trimester, third trimester, and postpartum. Infant washout samples were collected after birth. Elvitegravir and cobicistat were measured in plasma by a validated liquid chromatography with tandem mass spectrometry assay with a lower quantitation limit of 10 ng/ml. A two-tailed Wilcoxon signed-rank test (α = 0.10) was employed for paired within-participant comparisons.ResultsThirty pregnant women taking elvitegravir and cobicistat once-daily enrolled in the study. Compared with paired postpartum data, elvitegravir AUC0-24 was 24% lower in the second trimester [n = 14, P = 0.058, geometric mean ratios (GMR) = 0.76, 90% confidence interval (CI) 0.57-1.0] and 44% lower in the third trimester (n = 24, P = 0.0001, GMR = 0.56, 90% CI 0.42-0.73), while cobicistat AUC0-24 was 44% lower in the second trimester (n = 14, P = 0.0085, GMR = 0.56, 90% CI 0.37-0.85) and 59% lower in the third trimester (n = 24, P < 0.0001, GMR = 0.41, 90% CI 0.30-0.57). Median cord blood elvitegravir concentration was 540.6 ng/ml and the median ratio of cord blood to maternal plasma elvitegravir concentrations was 0.91.ConclusionStandard elvitegravir and cobicistat dosing during pregnancy results in significantly lower exposure which may increase the risk of virologic failure and mother-to-child transmission. Additional studies are needed to optimize elvitegravir and cobicistat dosing regimens in pregnant women.

Dataset Information

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

Objective

Design

Methods

Results

Conclusion

Publications

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

Similar Datasets

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