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Author Notes:

Correspondence: Edward P Acosta, Division of Clinical Pharmacology, University of Alabama at Birmingham, School of Medicine, 1670 University Blvd, Volker Hall, Room 258, Birmingham, AL 35294-0019, USA, Tel +1 205 934 2655, Fax +1 205 934 6201, Email eacosta@uab.edu.

The authors report no conflicts of interest in this work.

Subjects:

Research Funding:

This work was conducted with the support of grant OPP1002972 from the Bill and Melinda Gates Foundation, grant P30AI050409 by the Emory Center for AIDS Research funded through the National Institute of Allergy and Infectious Diseases, grant UL1RR025008 from the Atlanta Clinical and Translational Science Institute funded through the National Center for Research Resources, and grant U01AI103408-01 from the Women Interagency HIV Cohort Study.

AMJ received funding from the University of Alabama at Birmingham Office of Diversity and Equity by the Comprehensive Minority Student Development Program at University of Alabama at Birmingham.

Keywords:

  • emtricitabine
  • hormones
  • in vitro
  • pre-exposure prophylaxis
  • tenofovir

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

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Journal Title:

Journal of Experimental Pharmacology

Volume:

Volume 5

Publisher:

, Pages 55-64

Type of Work:

Article | Final Publisher PDF

Abstract:

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/10(6) for BC-3 and 77 versus 506 fmol/10(6) cells for TF-1; emtricitabine, 36 versus 12 fmol/10(6) for BC-3 and 75 versus 5 fmol/10(6) 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.

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© 2013 James et al, publisher and licensee Dove Medical Press Ltd.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-Noncommercial 3.0 Unported License (http://creativecommons.org/licenses/by-nc/3.0/).

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