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Endogenous Hormones and Antiretroviral Exposure in Plasma, Cervicovaginal Fluid, and Upper-Layer Packed Cells of Malawian Women Living with HIV

Authors
  • Nicol, Melanie R.1
  • Cottrell, Mackenzie L.2
  • Corbett, Amanda H.2
  • Chinula, Lameck3, 4
  • Tegha, Gerald4
  • Stanczyk, Frank Z.5
  • Hurst, Stacey6
  • Kourtis, Athena P.6
  • Tang, Jennifer H.3, 4
  • 1 Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota, USA.
  • 2 Division of Pharmacotherapy and Experimental Therapeutics, School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
  • 3 Department of Obstetrics and Gynecology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
  • 4 UNC Project Malawi, Lilongwe, Malawi.
  • 5 Department of Obstetrics and Gynecology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
  • 6 Division of Reproductive Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
Type
Published Article
Journal
AIDS Research and Human Retroviruses
Publisher
Mary Ann Liebert
Publication Date
Jul 31, 2020
Volume
36
Issue
8
Pages
641–646
Identifiers
DOI: 10.1089/aid.2019.0278
PMID: 32390454
PMCID: PMC7414802
Source
PubMed Central
Keywords
License
Green

Abstract

Overlap in metabolism pathways of endogenous female sex hormones and antiretroviral drugs may lead to altered exposure to these compounds. In a family planning clinic in Lilongwe, Malawi, blood, blood cell, and cervicovaginal fluid (CVF) samples from seventy-three HIV positive Malawian women taken in follicular and luteal menstrual phases were assessed for estradiol and progesterone by chemiluminescent immunoassay, and for antiretroviral concentration by liquid chromatography-mass spectrometry. In both follicular and luteal phases, estradiol concentrations were lower in women receiving efavirenz compared with women on non-efavirenz regimens or no antiretroviral therapy ( p < .01). Serum estradiol was moderately and negatively correlated with efavirenz plasma ( r = −0.36, p < .001) and CVF ( r = −0.50, p < .001) concentrations. Serum estradiol was a significant predictor of efavirenz CVF concentrations even after adjusting for efavirenz plasma concentrations ( p = .02). In upper-layer packed cells (ULPCs), tenofovir diphosphate (TFVdp) concentrations were similar between follicular and luteal phases and were not correlated with estradiol or progesterone concentrations. Tenofovir concentrations in CVF were not associated with menstrual cycle or serum hormone concentrations. In CVF and plasma, efavirenz concentrations were negatively correlated with serum estradiol concentrations, suggesting a modulatory effect of estradiol on efavirenz metabolism and/or transport processes, and/or an effect of efavirenz on the metabolism of estradiol. Differences in CVF persisted even after adjusting for plasma concentrations, suggesting a mechanism specific to the female genital compartment separate from absorption or hepatic metabolism. In contrast, TFVdp concentrations in ULPC were not influenced by endogenous estradiol or progesterone concentrations.

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