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

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 coppe...

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Published in:	PloS one 2020-03, Vol.15 (3), p.e0230473-e0230473
Main Authors:	Haddad, Lisa B, Swaims-Kohlmeier, Alison, Mehta, C Christina, Haaland, Richard E, Brown, Nakita L, Sheth, Anandi N, Chien, Hsin, Titanji, Kehmia, Achilles, Sharon L, Lupo, Davis, Hart, Clyde E, Ofotokun, Igho
Format:	Article
Language:	eng
Subjects:	Acetic acid Acquired immune deficiency syndrome Activation AIDS Analysis Biology and Life Sciences Birth control Blood Blood plasma CC chemokine receptors CCR5 protein CCR7 protein CD103 antigen CD38 antigen CD4 antigen Cell activation Chemokines Contraception Contraceptive drug implants Contraceptive drugs Contraceptives Copper Cytokines Data acquisition Disease control Disease prevention Disease transmission Engineering and Technology Epidemiology Etonogestrel Evaluation Flow cytometry Genital tract Granulocyte colony-stimulating factor Gynecology Health risks Histocompatibility antigen HLA HIV HIV (Viruses) Human immunodeficiency virus Immunological memory Infections Infectious diseases Interleukin 1 Intrauterine devices IUD Laboratories Leukocytes Leukocytes (mononuclear) Levonorgestrel Lymphocytes Lymphocytes T Markers Medicine Medicine and Health Sciences Medroxyprogesterone Medroxyprogesterone acetate Memory cells Menopause Menstruation Methods Nature Obstetrics Peripheral blood mononuclear cells Placement Progestin Public health Risk analysis Sexually transmitted diseases STD Studies T cells Transplants & implants Womens health
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Summary:	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. 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. 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. 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 (HLA-DR+, p = 0.01) or unchanged (CD38+, p = 0.45). Most CVL cytokine and chemokine concentrations were not signific
ISSN:	1932-6203 1932-6203