Effect of Progesterone Contraceptives on the Vaginal Microbiome

黄体酮避孕药对阴道微生物组的影响

• 批准号: 8588492
• 负责人: Jason Daniel Bell
• 金额: $ 8.3万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-22 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8588492
• 关键词: AIDS/HIV problem; Address; Affect; Africa South of the Sahara; Age; Animal Model; Area; Bacterial Infections; Bacterial Vaginosis; Businesses; Cervix Mucus; Characteristics; Clinical; Communities; Contraceptive Agents; Contraceptive Usage; Contraceptive methods; Data; Detection; Developing Countries; Devices; Discipline of obstetrics; Disease; Ecology; Ethnic Origin; Evaluation; Foundations; Genes; Government; Gynecologic; HIV; Health; High Prevalence; Hormonal; Implant; In Vitro; Individual; Infection; Intervention; Intrauterine Devices; Lead; Levonorgestrel; Life; Medroxyprogesterone 17-Acetate; Methods; Morbidity - disease rate; Mucosal Immunity; Outcome; Pattern; Pharmaceutical Preparations; Population; Prevalence; Progesterone; Race; Relative (related person); Reproductive Biology; Reproductive Tract Infections; Research; Research Personnel; Resistance; Resources; Ribosomal RNA; Risk; Sexually Transmitted Diseases; Surface; Swab; Testing; Time; Toll-like receptors; Unplanned pregnancy; Unwanted pregnancy; Vagina; Vertical Disease Transmission; Virus Shedding; Woman; adaptive immunity; aged; cohort; hormonal contraception; innovation; microbial; microbial community; microbiome; mortality; prevent; public health relevance; pyrosequencing; reproductive; reproductive epidemiology; transmission process

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.

描述（由申请人提供）：在全球范围内，安全有效避孕的需求大量未得到满足。世界上避孕需求未得到满足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，在艾滋病毒感染妇女中，这些方法不需要增加使用者获得疾病的风险。第二，在HIV+妇女中，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。这种增长的确切机制尚未明确确定。有些人认为阴道表面积的变化或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。阴道微生物组在维持生殖道健康方面很重要，并提供了对感染和细菌定植的防御。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阴道微生物组的变化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，与非激素方法相比，激素避孕导致阴道微生物组的有益变化，降低了生殖道感染的风险。我们将研究与非激素IUD使用者的参考人群相比，HIV女性阴道微生物组的变化归因于激素避孕药（IUD，植入物，注射）。将使用三个时间点（0、6和12个月）的阴道拭子来确定随时间推移对阴道微生物组的影响。我们将通过以下方式实现这一目标：（a）使用高通量16 S rRNA编码基因焦磷酸测序表征基线阴道微生物组;（B）定义并比较现代避孕开始后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孕激素避孕方法对艾滋病毒感染妇女阴道微生物群的影响。了解阴道微生物组的改变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。