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The role of menopause in tenofovir diphosphate and emtricitabine triphosphate concentrations in cervical tissue.


ABSTRACT: Objective: Although postmenopausal (post-M) women have behavioral and biological risk factors for HIV infection, the activity of preexposure prophylaxis (PrEP) agents in older adults has not been well studied.

Design: We used an ex-vivo approach to compare the tissue concentrations of tenofovir (TFV) diphosphate (TFVdp) and emtricitabine (FTC) triphosphate (FTCtp) in cervical tissues from premenopausal (pre-M) and post-M women.

Method: Cervical explants from 16 pre-M and 11 post-M women were incubated in 10-300??g/ml TFV or FTC for 24?h. Explants were then snap frozen in liquid nitrogen and stored until analysis. TFVdp and FTCtp were quantified using tandem liquid chromatography-mass spectrometry.

Results: Active metabolite concentrations of TFVdp were more than nine-fold lower in post-M explants (P?
Conclusion: These findings could have implications in the use of nucleotide-based PrEP strategies targeted to older women. If validated in vivo, lower exposures of active nucleoside/tide metabolites could mean post-M women need higher doses of TFV-based PrEP to achieve protective efficacy.

SUBMITTER: Nicol MR 

PROVIDER: S-EPMC7719012 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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The role of menopause in tenofovir diphosphate and emtricitabine triphosphate concentrations in cervical tissue.

Nicol Melanie R MR   Brewers Lindsey M LM   Kashuba Angela D M ADM   Sykes Craig C  

AIDS (London, England) 20180101 1


<h4>Objective</h4>Although postmenopausal (post-M) women have behavioral and biological risk factors for HIV infection, the activity of preexposure prophylaxis (PrEP) agents in older adults has not been well studied.<h4>Design</h4>We used an ex-vivo approach to compare the tissue concentrations of tenofovir (TFV) diphosphate (TFVdp) and emtricitabine (FTC) triphosphate (FTCtp) in cervical tissues from premenopausal (pre-M) and post-M women.<h4>Method</h4>Cervical explants from 16 pre-M and 11 po  ...[more]

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