The pharmacokinetics, safety and efficacy of tenofovir and emtricitabine in HIV-1-infected pregnant women

Colbers, Angela P. H., Hawkins, David A., Gingelmaier, Andrea, Kabeya, Kabamba, Rockstroh, Juergen K., Wyen, Christopher, Weizsaecker, Katharina, Sadiq, S. Tariq, Ivanovic, Jelena, Giaquinto, Carlo, Taylor, Graham P., Molto, Jose and Burger, David M. (March 2013): The pharmacokinetics, safety and efficacy of tenofovir and emtricitabine in HIV-1-infected pregnant women. In: AIDS, Vol. 27, No. 5: pp. 739-748

Abstract

Objective: To describe the pharmacokinetics of tenofovir and emtricitabine in the third trimester of pregnant HIV-infected women and at postpartum. Design: A nonrandomized, open-label, multicentre phase IV study in HIV-infected pregnant women recruited from HIV treatment centres in Europe. Methods: HIV-infected pregnant women treated with the nucleotide/nucleoside analogue reverse transcriptase inhibitors (NRTIs) tenofovir disoproxil fumarate (TDF 300 mg; equivalent to 245 mg tenofovir disoproxil) and/or emtricitabine (FTC 200 mg) were included in the study. Twenty-four-hour pharmacokinetic curves were recorded in the third trimester (preferably week 33) and postpartum (preferably week 4-6). Collection of a cord blood sample and maternal sample at delivery was optional. Pharmacokinetic parameters were calculated using WinNonlin software version 5.3. Statistical analysis was conducted using SPSS version 16.0. Results: Thirty-four women were included in the analysis. Geometric mean ratios of third trimester vs. postpartum 90% confidence interval (CI)] were 0.77 (0.71-0.83) for TDF area under the curve (AUC(0-24 h)); 0.81 (0.68-0.96) for TDF C-max and 0.79 (0.70-0.90) for TDF C-24 h and 0.75 (0.68-0.82) for FTC AUC(0-24 h); and 0.87 (0.77-0.99) for FTC C-max and 0.77 (0.52-1.12) for FTC C-24 h. The viral load close to delivery was less than 200 copies/ml in all but one patient, the average gestational age at delivery was 38 weeks. All children were tested HIV-negative and no congenital abnormalities were reported. Conclusion: Although pharmacokinetic exposure of the NRTIs TDF and FTC during pregnancy is approximately 25% lower, this was not associated with virological failure in this study and did not result in mother-to-child transmission. (C) 2013 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins AIDS 2013, 27:739-748

• Item Type: Journal article
• Form of publication: Publisher's Version
• Keywords: combination antiretroviral therapy; emtricitabine; HIV; mother-to-child transmission; pharmacokinetics; pregnancy; tenofovir
• Faculties: Medicine
• Subjects: 600 Technology > 610 Medicine and health
• ISSN: 0269-9370
• Place of Publication: 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
• Alliance/National Licence: This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.
• Language: English