MECHANISMS AND COFACTORS OF HIV TRANSMISSION TO WOMEN

描述(申请人提供)：女性感染HIV-1是一种相对罕见的性接触HIV-1的结果。每个女性的风险可能不同，同一个女性在不同的暴露期间风险也可能不同。易感性是由一系列复杂的因素决定的，包括妇女接触的病毒的数量和性质、个体宿主遗传因素以及接触时存在的多种可改变的生物辅助因素。在这项计划项目拨款中，我们建议研究生物辅助因素增加妇女感染HIV-1的易感性的机制。拟议的研究将包括多个高危群体的妇女：性工作者、孕妇/产后妇女和处于HIV-1不和谐关系中的妇女。具体地说，我们将研究以下因素的作用：1)怀孕和产后的影响(项目1)；2)阴道菌群和特定的细菌感染(项目2)；3)先天免疫因素，包括它们与激素和生殖道感染有关的因素(项目3)；以及4)反复接触艾滋病毒-1后诱导的粘膜艾滋病毒-1抗体(项目4)对妇女感染艾滋病毒-1的易感性。对于这些研究，我们将利用我们的研究团队西雅图/肯尼亚合作研究小组在过去约15年中开发的队列研究、合作伙伴关系和基础设施。我们的研究小组包括病毒学家、免疫学家、细菌学家、流行病学家、统计学家和临床科学家，有着长期而富有成效的合作历史，并以专注于女性的翻译研究而闻名。在这里，我们将在此基础上，在该计划拨款内开展多个协作项目。我们预计，这些项目中的每一个都将借鉴团队中其他人的专业知识，在某些情况下，还将包括解决同一人群中的协同生物学问题的平行研究。

DESCRIPTION (provided by applicant): HIV-1 infection of women is a relatively rare outcome of sexual exposure to HIV-1. The risk may vary for each woman, and it may also vary for the same woman during different exposures. Susceptibility is determined by a complex set of factors, including the amount and properties of the virus to which a woman is exposed, individual host genetic factors, as well as multiple modifiable biological cofactors present at the time of exposure. In this program project grant, we proposed to examine the mechanisms by which biological cofactors increase susceptibility of women to HIV-1. The proposed studies will include women in multiple high-risk groups: sex workers, pregnant/postpartum women and women in HIV-1 discordant relationships. Specifically, we will examine the role of: 1) pregnancy and the postpartum effects (Project 1); 2) vaginal flora and specific bacterial infections (Project 2); 3) innate immune factors, including as they relate to hormones and genital tract infections (Project 3); and 4) mucosal HIV-1 antibodies induced in response to repeated HIV-1 exposure (Project 4) on susceptibility to HIV-1 infection in women. For these studies, we will take advantage of cohort studies, collaborative partnerships and infrastructure developed by our research team, the Seattle/Kenya collaborative research group, over the past ~ 15 years. Our research group, which includes virologists, immunologists, bacteriologists, epidemiologist, statisticians and clinical scientists, has a long and productive history of collaboration, and is known for its focus on translational research in women. Here we will build on that foundation to conduct multiple collaborative projects within this program grant. We expect that each of these projects will draw on the expertise of others in the team, and in some cases, will include parallel studies that address synergistic biological questions in the same populations.