Back to Journals » Journal of Experimental Pharmacology » Volume 5

Uptake of tenofovir and emtricitabine into non-monocytic female genital tract cells with and without hormonal contraceptives

Authors James, King J, Ofotokun, Sheth A, Acosta E

Received 16 March 2013

Accepted for publication 10 April 2013

Published 1 August 2013 Volume 2013:5 Pages 55—64

DOI https://doi.org/10.2147/JEP.S45308

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2



Amanda Marie James,1 Jennifer R King,1 Ighovwerha Ofotokun,2 Anandi N Sheth,2 Edward P Acosta1

1Division of Clinical Pharmacology, 2Emory University School of Medicine, Department of Medicine, Division of Infectious Diseases, The University of Alabama at Birmingham, Birmingham, AL, USA

Background: Pre-exposure prophylaxis is becoming a strategic component used to control the human immunodeficiency virus (HIV-1) epidemic. The goal of this study was to characterize intracellular uptake of tenofovir and emtricitabine using five surrogate cell lines of the female genital tract and determine whether exogenous hormones influence their uptake.
Methods: Surrogate cell lines, ie, THP-1 (representing macrophages), BC-3 (CD8+), Ect1/E6E7 (squamous epithelial), HeLa (CD4+), and TF-1 (dendritic), were incubated for one hour with tenofovir and emtricitabine to assess uptake. In separate experiments, ethinyl estradiol (EE) and etonogestrel (ET) individually and together (EE/ET) were added prior to, simultaneously, and after incubation. Intracellular phosphorylated tenofovir and emtricitabine were quantified using validated tandem mass spectrometry methods.
Results: HeLa and Ect1/E6E7 cells showed significantly increased uptake relative to THP-1 controls for both antiretrovirals. Individually, ethinyl estradiol and etonogestrel significantly altered antiretroviral uptake across all cell lines, except Ect1/E6E7 for tenofovir and HeLa for emtricitabine. Cellular uptake of tenofovir and emtricitabine in BC-3 and TF-1 cells were significantly lower when dosed one hour prior to EE/ET administration compared with each antiretroviral administered in the absence of EE/ET (tenofovir, 80 versus 470 fmol/106 for BC-3 and 77 versus 506 fmol/106 cells for TF-1; emtricitabine, 36 versus 12 fmol/106 for BC-3 and 75 versus 5 fmol/106 cells for TF-1; P < 0.01 for each).
Conclusion: These data suggest that intracellular uptake of tenofovir and emtricitabine within the female genital tract varies by cell type and in the presence of hormonal contraceptives. The potential clinical implications of these findings should be further evaluated in vivo.

Keywords: pre-exposure prophylaxis, tenofovir, emtricitabine, in vitro, hormones

Creative Commons License © 2013 The Author(s). This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.