HIV/AIDS is the leading cause of death and disease worldwide for women in their reproductive years, highlighting the importance of understanding the effects of contraceptives on HIV-1 risk. The World Health Organization (WHO) recently recommended that more research be done on the effects of exogenous hormones and contraceptives, including intrauterine devices (IUDs), on the female reproductive tract (FRT). In 2007, more than 160 million women were using IUDs globally, yet the WHO has concluded that data regarding IUD use and risk of HIV-1 infection are limited. The upper FRT has been minimally studied in the context of HIV transmission. We have demonstrated that the levonorgestrel (LNG) intrauterine system (LNG-IUD or Mirena) has pro-inflammatory effects on the upper FRT;an injectable hormonal contraceptive, depo-medroxyprogesterone acetate (DMPA) had similar but less pronounced effects on the same parameters. Given these findings, we hypothesize that the presence of the IUD foreign body results in changes in the upper FRT that can increase risk of HIV-1 infection. We will test this hypothesis by recruiting four groups o reproductive aged healthy women [Group A-LNG-IUD users;Group B-copper (non-hormonal) IUD users;Group C-users of LNG-containing oral contraceptives (OC);Group D-non-users of IUDs, OCs or injectable hormones]. We will collect a comprehensive set of FRT specimens synchronized to the mid-secretory phase from participants for the following Specific Aims: 1. To determine the effects of IUDs and LNG on the immune microenvironment of the FRT 2. To determine whether IUDs and LNG alter susceptibility of FRT immune cells to HIV-1 infection 3. To determine whether IUDs and LNG modulate the pyroptotic susceptibility of T cells from the FRT. Results from these aims will provide a comprehensive assessment of biological effects of IUDs and LNG on the upper FRT, and will directly address the knowledge gap surrounding effects of IUDs on parameters relevant to HIV-1 susceptibility.
These studies are relevant to public health due to knowledge gaps surrounding the effects of commonly used contraceptives on a woman's risk of getting HIV. The results of this study will provide detailed novel information about the effects of intrauterine devices and oral contraceptives on the immunology of the female reproductive tract. This information will be useful for assessing the risk of these products in areas with high HIIV prevalence, and in designing new HIV prevention strategies in the future.