Effect of Progesterone Contraceptives on the Vaginal Microbiome

描述（由申请人提供）：在全球范围内，对安全和有效避孕的需求仍未得到满足。世界上未满足避孕需求最多的地区也是艾滋病毒/艾滋病负担最重的地区。这是一项艰巨的挑战。首先，在感染艾滋病毒的妇女中，这些方法不需要增加使用者感染这种疾病的风险。其次，在艾滋病毒阳性的女性中，这些方法不需要增加病毒脱落的风险。研究表明，使用激素避孕会增加感染艾滋病毒的风险。导致这种增加的确切机制尚未得到明确确定。一些人认为阴道表面面积的变化或toll样受体的变化，而另一些人则认为阴道微生物群的改变和由此产生的细菌性阴道病样状态可能是罪魁祸首。阴道微生物群在维持生殖道健康和提供防御感染和细菌定植方面很重要。迫切需要了解阴道微生物组的变化，以确定现代避孕方法是否会改变女性感染艾滋病毒的风险。目前尚不清楚现代避孕方法是否通过改变阴道微生物群来改变生殖道感染的风险，但体外和动物模型的数据表明，这可能是一个重要的机制。我们的中心假设是，与非激素避孕方法相比，激素避孕会导致阴道微生物群的有益变化，从而降低生殖道感染的风险。我们将研究与非激素宫内节育器使用者的参考人群相比，激素避孕药（宫内节育器，植入物，注射）导致的HIV-妇女阴道微生物组的变化。将使用三个时间点（0、6和12个月）的阴道拭子来确定随着时间的推移对阴道微生物组的影响。我们将通过(a)使用高通量16S rrna编码基因焦磷酸测序来表征基线阴道微生物组；(b)定义和比较在现代避孕开始后6个月和12个月阴道微生物组的变化。这项创新的研究将有助于了解黄体酮避孕方法对艾滋病毒妇女阴道微生物群的影响。了解阴道微生物组的变化可能有助于更好地了解这些激素避孕对艾滋病毒感染的影响。

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.