Abstract
BackgroundHormonal contraceptives, particularly depot medroxyprogesterone acetate (DMPA), have been reported to be associated with substantially enhanced HIV acquisition; however, the biological mechanisms of this risk remain poorly understood. We aimed to investigate the effects of different hormonal contraceptives on the expression of the HIV co-receptors, CXCR4 and CCR5, on female endocervical and peripheral blood T cells.MethodsA total of 59 HIV-negative women were enrolled, including 15 initiating DMPA, 28 initiating a levonorgestrel-releasing intrauterine device (LNG-IUD) and 16 initiating an etonogestrel (ETG)-delivering vaginal ring. Peripheral blood and endocervical cytobrush specimens were collected at enrollment and 3–4 weeks after contraception initiation to analyze the expression of CXCR4 and CCR5, on CD4+ and CD8+ T cells using flow cytometry.ResultsAdministration of DMPA increased the percentages of CD4+ and CD8+ T cells expressing CCR5 in the endocervix but not in the peripheral blood. Administration of the LNG-IUD or the ETG vaginal ring did not affect the percentages of T lymphocytes expressing CXCR4 or CCR5 in the female cervix or peripheral blood.ConclusionsIncrease in the percentage of endocervical T cells expressing CCR5 upon DMPA exposure provides a plausible biological explanation for the association between DMPA use and an elevated risk of HIV infection.
Highlights
Hormonal contraceptives, depot medroxyprogesterone acetate (DMPA), have been reported to be associated with substantially enhanced HIV acquisition; the biological mechanisms of this risk remain poorly understood
Fifteen patients chose DMPA and 150 mg of the drug was given intramuscularly at the time of study entry; 28 chose the levonorgestrel-releasing intrauterine device (LNG-IUD) (Mirena, Bayer Pharmaceuticals, Berlin, Germany), which was inserted under sterile conditions at the initial study visit; and 16 chose the ETG vaginal ring (NuvaRing, Merck & Co., Kenilworth, NJ), which was inserted by patient or provider with ring placement verified by the provider after sample collection at the first study visit
These two women were both treated with DMPA and the flow cytometry results of them were shown in Additional file 1: Figure S1
Summary
Depot medroxyprogesterone acetate (DMPA), have been reported to be associated with substantially enhanced HIV acquisition; the biological mechanisms of this risk remain poorly understood. There is a significant concomitant risk for vertical transmission in HIV-infected women, those who are not on antiretroviral therapies [2]. Long-acting contraceptive methods include injectables, Li et al Reproductive Biology and Endocrinology (2019) 17:26 implants, hormone-releasing intrauterine systems and vaginal rings. DMPA is one of the most commonly used hormonal contraceptive methods in the world, in Sub-Saharan Africa, and the only injectable contraceptive currently available in the United States [9]. The levonorgestrel-releasing intrauterine device (LNG-IUD) containing 52 mg LNG is a highly effective, progestin-only, long-acting and reversible contraceptive method that is regaining popularity in the United States [10]. The NuvaRing, an etonogestrel (ETG)-delivering vaginal ring used over a 4-week cycle, is an effective and well-tolerated method of contraception that releases 15 μg of ethinyl estradiol and 120 μg of ETG daily [11]
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