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Author Notes:

Lisa B. Haddad, E-mail: lbhadda@emory.edu

Manish Sagar, Editor

Thank you to Tammy Evans-Strickfaden for assistance in the development of laboratory procedures and processes leveraged for this evaluation and Cheng Chen and Kai-Hua Chi for conducting the multiplex PCR assessment.

No authors have competing interests.

Subject:

Research Funding:

This study was supported by the U.S. Centers for Disease Control and Prevention, the NIH NICHD K23HD078153-01A1 (L.B.H) and the Emory University Center for AIDS research (P30AI050409).

Keywords:

  • Science & Technology
  • Multidisciplinary Sciences
  • Science & Technology - Other Topics
  • DEPOT MEDROXYPROGESTERONE ACETATE
  • COLONY-STIMULATING FACTOR
  • HORMONAL CONTRACEPTION
  • INTRAUTERINE-DEVICE
  • VAGINAL MICROBIOTA
  • HIV ACQUISITION
  • CUTTING EDGE
  • WOMEN
  • LUNG
  • PROTECTION

Impact of etonogestrel implant use on T-cell and cytokine profiles in the female genital tract and blood

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Journal Title:

PLOS ONE

Volume:

Volume 15, Number 3

Publisher:

, Pages e0230473-e0230473

Type of Work:

Article | Final Publisher PDF

Abstract:

Background While prior epidemiologic studies have suggested that injectable progestin-based contraceptive depot medroxyprogesterone acetate (DMPA) use may increase a woman’s risk of acquiring HIV, recent data have suggested that DMPA users may be at a similar risk for HIV acquisition as users of the copper intrauterine device and levonorgestrel implant. Use of the etonogestrel Implant (Eng-Implant) is increasing but there are currently no studies evaluating its effect on HIV acquisition risk. Objective Evaluate the potential effect of the Eng-Implant use on HIV acquisition risk by analyzing HIV target cells and cytokine profiles in the lower genital tract and blood of adult premenopausal HIV-negative women using the Eng-Implant. Methods We prospectively obtained paired cervicovaginal lavage (CVL) and blood samples at 4 study visits over 16 weeks from women between ages 18–45, with normal menses (22–35 day intervals), HIV uninfected with no recent hormonal contraceptive or copper intrauterine device (IUD) use, no clinical signs of a sexually transmitted infection at enrollment and who were medically eligible to initiate Eng-Implant. Participants attended pre-Eng-Implant study visits (week -2, week 0) with the Eng-Implant inserted at the end of the week 0 study visit and returned for study visits at weeks 12 and 14. Genital tract leukocytes (enriched from CVL) and peripheral blood mononuclear cells (PBMC) from the study visits were evaluated for markers of activation (CD38, HLA-DR), retention (CD103) and trafficking (CCR7) on HIV target cells (CCR5+CD4+ T cells) using multicolor flow cytometry. Cytokines and chemokines in the CVL supernatant and blood plasma were measured in a Luminex assay. We estimated and compared study endpoints among the samples collected before and after contraception initiation with repeated-measures analyses using linear mixed models. Results Fifteen of 18 women who received an Eng-Implant completed all 4 study visits. The percentage of CD4+ T cells in CVL was not increased after implant placement but the percentage of CD4+ T cells expressing the HIV co-receptor CCR5 did increase after implant placement (p = 0.02). In addition, the percentage of central memory CD4+ T-cells (CCR7+) in CVL increased after implant placement (p = 0.004). The percentage of CVL CD4+, CCR5+ HIV target cells expressing activation markers after implant placement was either reduced (HLADR+, p = 0.01) or unchanged (CD38+, p = 0.45). Most CVL cytokine and chemokine concentrations were not significantly different after implant placement except for a higher level of the soluble lymphocyte activation marker (sCD40L; p = 0.04) and lower levels of IL12p70 (p = 0.02) and G-CSF (p<0.001). In systemic blood, none of the changes noted in CVL after implant placement occurred except for decreases in the percentage CD4 T-cells expressing HLA-DR+ T cells (p = 0.006) and G-CSF (p = 0.02). Conclusions Eng-Implant use was associated with a moderate increase in the availability of HIV target cells in the genital tract, however the percentage of these cells that were activated did not increase and there were minimal shifts in the overall immune environment. Given the mixed nature of these findings, it is unclear if these implant-induced changes alter HIV risk.

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This is an Open Access work distributed under the terms of the Creative Commons Universal : Public Domain Dedication License (https://creativecommons.org/publicdomain/zero/1.0/).
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