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Endogenous Hormones and Antiretroviral Exposure in Plasma, Cervicovaginal Fluid, and Upper-Layer Packed Cells of Malawian Women Living with HIV.
AIDS Res Hum Retroviruses. 2020 Aug; 36(8):641-646.AR

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.

Authors+Show Affiliations

Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota, USA.Division of Pharmacotherapy and Experimental Therapeutics, School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.Division of Pharmacotherapy and Experimental Therapeutics, School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.Department of Obstetrics and Gynecology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. UNC Project Malawi, Lilongwe, Malawi.UNC Project Malawi, Lilongwe, Malawi.Department of Obstetrics and Gynecology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.Division of Reproductive Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.Division of Reproductive Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.Department of Obstetrics and Gynecology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. UNC Project Malawi, Lilongwe, Malawi.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32390454

Citation

Nicol, Melanie R., et al. "Endogenous Hormones and Antiretroviral Exposure in Plasma, Cervicovaginal Fluid, and Upper-Layer Packed Cells of Malawian Women Living With HIV." AIDS Research and Human Retroviruses, vol. 36, no. 8, 2020, pp. 641-646.
Nicol MR, Cottrell ML, Corbett AH, et al. Endogenous Hormones and Antiretroviral Exposure in Plasma, Cervicovaginal Fluid, and Upper-Layer Packed Cells of Malawian Women Living with HIV. AIDS Res Hum Retroviruses. 2020;36(8):641-646.
Nicol, M. R., Cottrell, M. L., Corbett, A. H., Chinula, L., Tegha, G., Stanczyk, F. Z., Hurst, S., Kourtis, A. P., & Tang, J. H. (2020). Endogenous Hormones and Antiretroviral Exposure in Plasma, Cervicovaginal Fluid, and Upper-Layer Packed Cells of Malawian Women Living with HIV. AIDS Research and Human Retroviruses, 36(8), 641-646. https://doi.org/10.1089/AID.2019.0278
Nicol MR, et al. Endogenous Hormones and Antiretroviral Exposure in Plasma, Cervicovaginal Fluid, and Upper-Layer Packed Cells of Malawian Women Living With HIV. AIDS Res Hum Retroviruses. 2020;36(8):641-646. PubMed PMID: 32390454.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Endogenous Hormones and Antiretroviral Exposure in Plasma, Cervicovaginal Fluid, and Upper-Layer Packed Cells of Malawian Women Living with HIV. AU - Nicol,Melanie R, AU - Cottrell,Mackenzie L, AU - Corbett,Amanda H, AU - Chinula,Lameck, AU - Tegha,Gerald, AU - Stanczyk,Frank Z, AU - Hurst,Stacey, AU - Kourtis,Athena P, AU - Tang,Jennifer H, Y1 - 2020/06/09/ PY - 2020/5/12/pubmed PY - 2020/5/12/medline PY - 2020/5/12/entrez KW - adherence KW - antiretrovirals KW - efavirenz KW - estradiol KW - hormones KW - tenofovir SP - 641 EP - 646 JF - AIDS research and human retroviruses JO - AIDS Res. Hum. Retroviruses VL - 36 IS - 8 N2 - 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. SN - 1931-8405 UR - https://www.unboundmedicine.com/medline/citation/32390454/Endogenous_Hormones_and_Antiretroviral_Exposure_in_Plasma,_Cervicovaginal_Fluid,_and_Upper-Layer_Packed_Cells_of_Malawian_Women_Living_with_HIV L2 - https://www.liebertpub.com/doi/10.1089/AID.2019.0278?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -
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