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

Colbers, Angela P.H.a; Hawkins, David A.b; Gingelmaier, Andreac; Kabeya, Kabambad; Rockstroh, Jürgen K.e; Wyen, Christopherf; Weizsäcker, Katharinag; Sadiq, S. Tariqh; Ivanovic, Jelenai; Giaquinto, Carloj; Taylor, Graham P.k; Moltó, Josél; Burger, David M.a; on behalf of the PANNA network

doi: 10.1097/QAD.0b013e32835c208b
Clinical Science

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 (AUC0–24 h); 0.81 (0.68–0.96) for TDF Cmax and 0.79 (0.70–0.90) for TDF C24 h and 0.75 (0.68–0.82) for FTC AUC0–24 h; and 0.87 (0.77–0.99) for FTC Cmax and 0.77 (0.52–1.12) for FTC C24 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.

aRadboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

bChelsea & Westminster Hospital, London, UK

cKlinikum der Universität München, Frauenklinik Innenstadt, Munich, Germany

dSaint-Pierre University Hospital, Brussels, Belgium

eUniversity of Bonn, Bonn

fUniversity of Cologne, Cologne

gKlinik für Geburtsmedizin, Charité Universitätsmedizin, Berlin, Germany

hSt. George's, University of London, London, UK

iNational Institute for Infectious Diseases ‘L. Spallanzani’, Rome

jUniversity of Padua, Padova, Italy

kImperial College Healthcare NHS Trust, London, UK

lHospital Universitari Germans Trias I Pujol, Badalona, Spain.

Correspondence to Angela Colbers, MSc, Department of Pharmacy, Radboud University Nijmegen Medical Centre, Geert Grooteplein Zuid 10, 6525 GA Nijmegen, The Netherlands. Tel: +31 24 3616405; fax: +31 24 3668755; e-mail: a.colbers@akf.umcn.nl

Received 18 September, 2012

Revised 22 October, 2012

Accepted 31 October, 2012

© 2013 Lippincott Williams & Wilkins, Inc.