Abstract
Globally, HIV/AIDS is a leading cause of morbidity worldwide among reproductive-aged cisgender women, highlighting the importance of understanding effects of contraceptives on HIV-1 risk. Some observational studies suggest there may be an increased risk of HIV-1 acquisition among women using the long-acting injectable progestin contraceptive, depo-medroxyprogesterone acetate. The potential mechanism of this susceptibility is unclear. There are few data on the role of the upper female reproductive tract in HIV-1 transmission, and the mechanisms of HIV-1 infection are likely to differ in the upper compared to the lower reproductive tract due to differences in tissue composition and variable effects of sex steroids on mucosal immune cell distribution and activity. In this study, we measured the susceptibility of mucosal immune cells from the upper female reproductive tract to HIV-1 entry using the virion-based HIV-1 fusion assay in samples from healthy female volunteers. We studied 37 infectious molecular clones for their ability to fuse to cells from endometrial biopsies in three participants and found that subtype (B or C) and origin of the virus (transmitted founder or chronic control) had little influence on HIV-1 fusion susceptibility. We studied the effect of contraceptives on HIV-1 susceptibility of immune cells from the cervix, endometrium and peripheral blood by comparing fusion susceptibility in four groups: users of the copper intrauterine device (IUD), levonorgestrel-containing oral contraceptive, levonorgestrel-containing IUD and unexposed controls (n = 58 participants). None of the contraceptives was associated with higher rates of HIV-1 entry into female reproductive tract cells compared to control samples from the mid-luteal phase.
Highlights
An estimated 14.3% of women of reproductive age use intrauterine devices (IUDs) globally [1]
To illustrate replicate-level results generated by the fusion assay, for an endometrial biopsy sample and a blood sample, each from a single control participant not included in subsequent analyses, we present the observed distribution of immune cells (Cj / Ctotal, j = 1,2,. . .,12) and fusion susceptibility (FS) prevalence by phenotype (Fj / Ctotal, j = 1,2,. . .,12) using bar graphs
Our immunostaining panel could phenotype most of the immune cells that supported NL-104F4 fusion as evidenced by the very low number of fused cells not identified by our panel (Fig 1B)
Summary
An estimated 14.3% of women of reproductive age use intrauterine devices (IUDs) globally [1]. In 2007 and 2012, the World Health Organization (WHO) convened technical panels to discuss hormonal contraceptives, IUD use and HIV-1 risk [2, 3]. They concluded that none of the existing prospective studies found an association between IUD use and HIV-1 acquisition, but the numbers of studies, and of observations of IUD-users, were small [4,5,6]. The panel concluded: “Current evidence suggests that the use of the copper IUD does not increase the risk of HIV-1 acquisition. The 2012 panel stressed the need for ongoing research to evaluate the effects of hormonal contraceptives on HIV-1 acquisition risk [7]
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