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

Melanie R. Nicol, MacKenzie L. Cottrell, Amanda H. Corbett, Lameck Chinula, Gerald Tegha, Frank Z. Stanczyk, Stacey Hurst, Athena P. Kourtis, Jennifer H. Tang

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)641-646
Number of pages6
JournalAIDS Research and Human Retroviruses
Volume36
Issue number8
DOIs
StatePublished - Aug 2020

Bibliographical note

Funding Information:
This work was supported by funding from the Fogarty International Center (K01-TW009657 to J.H.T.), the National Institute of Allergy and Infectious Diseases (K08AI134262 to M.R.N., P30AI050410 to UNC CFAR), the Bill & Melinda Gates Foundation (no. OPP1090837), United States Agency for International Development (USAID) (no. AID-OAA-A-15-00045), and the U.S. Centers for Disease Control and Prevention (nos. U48DP001944 and 200-2015-M-63021).

Keywords

  • adherence
  • antiretrovirals
  • efavirenz
  • estradiol
  • hormones
  • tenofovir

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