Effect of Progesterone Contraceptives on the Vaginal Microbiome

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DESCRIPTION (provided by applicant): Globally there is a large unmet need for safe and effective contraception. The areas in the world with the highest unmet needs for contraception are also areas with greatest burden of HIV/AIDS. This represents a difficult challenge. First, in HIV- women these methods need to not increase the user's risk of acquiring the disease. Second, in HIV+ women these methods need to not increase the risk of viral shedding. Studies have suggested that the use of hormonal contraception increases the risk of HIV acquisition. The exact mechanism of how this increase may result has not been clearly identified. Some have suggested changes in vaginal surface area or changes in the Toll-like receptors while others have postulated that alterations to the vaginal microbiota and a resultant bacterial-vaginosis-like state may the culprit. The vaginal microbiome is important in maintaining reproductive tract health and provides defense against the acquisition of infection and bacterial colonization. Understanding changes in the vaginal microbiome is urgently needed to determine whether modern contraceptive methods modify a woman's risk for HIV. It is unknown whether modern contraceptive methods alter the risk for reproductive tract infections via changes in the vaginal microbiome, but data from in vitro and animal models suggest that this may be an important mechanism. Our central hypothesis is that hormonal contraception leads to beneficial changes in the vaginal microbiome that reduce the risk of incident reproductive tract infection when compared with non- hormonal methods. We will examine changes in the vaginal microbiome of HIV- women attributable to hormonal contraceptives (IUD, implant, shot) compared with the reference population of non-hormonal IUD users. Vaginal swabs from three time points (0, 6 and 12-months) will be used to define the impact on the vaginal microbiome over time. We will accomplish this by (a) characterizing the baseline vaginal microbiome using high-throughput 16S rRNA-encoding gene pyrosequencing; and (b) defining and comparing alterations to the vaginal microbiome at 6- and 12-months following modern contraceptive initiation. This innovative research will help understand the impact of progesterone contraceptive methods on the vaginal microbiota in HIV- women. Understanding the alterations to the vaginal microbiome may help to better understand the impact that these hormonal contraception's have on HIV acquisition.