Incidence, timing and cofactors that contribute to the high risk of HIV-1 Infect

怀孕和产后期与艾滋病毒-1的风险增加有关。在非洲，那里 HIV-1血清阳性率和生育率都很高，怀孕/产后期可能是 哪种HIV-1获得者对妇女感染HIV-1有很大贡献。怀孕、分娩和 产后期与荷尔蒙、生殖器粘膜和生殖器菌群的变化有关，这些变化可能 易感染HIV-1。项目1将招募2,000名未感染艾滋病毒的妇女 孕期及产后9个月随访，以确定HIV-1发病的危险因素及相关因素。女人 将感染HIV-1的女性与没有感染的女性进行比较，以确定生殖器联合感染的作用， 溃疡，分娩方式，哺乳，伴侣特征，阴道菌群变化，HSV-2，生殖器 先天免疫因素，以及全身免疫激活对HIV-1传播的影响。此外，在 孕期和产后的辅助因素可能会影响对HIV-1的易感性。因此，在一个 我们将比较100名女性的生殖器先天免疫因子和全身细胞免疫 在怀孕期间、产后早期和产后后期纵向激活。这些比较将 提供机会来确定生殖道在这一动态变化时期的变化模式 在女人身上。在量化混合感染中，粘膜先天免疫反应和系统细胞免疫 激活，我们将能够确定这些重要决定因素之间的相互作用 影响对HIV-1易感性的相互关联的区域(共同感染、粘膜固有环境、系统细胞)。 项目1将与项目2(阴道菌群变化对艾滋病毒-1传播的影响)建立科学联系， 项目3(将涉及项目1队列中妇女的细胞因子图谱分析)和项目4 (未感染HIV-1的妇女与HIV-1感染者的适应性体液粘膜反应)。因为. 女性生殖器生态系统的复杂性以及可能改变其易感性的各种因素 关于艾滋病毒-1，每个项目将侧重于可能改变艾滋病毒-1传播的补充因素。一起， 这些将导致对妇女在不同重要群体中的传播进行多方面的评估 有感染HIV-1风险的妇女(怀孕/产后、女性性工作者和不和谐的夫妇)， 可以想象，HIV-1易感性的一些共同因素是相同的，但在其他因素中是不同的。

Pregnancy and the postpartum period have been associated with increased risk of HIV-1. In Africa, where both HIV-1 seroprevalence and fertility rates are high, the pregnancy/postpartum period may be one in which HIV-1 acquisition contributes substantially to HIV-1 in women. Pregnancy, delivery, and the postpartum period are associated with hormonal, genital mucosal, and genital flora changes that could predispose to acquisition of HIV-1. Project 1 will enroll 2,000 HIV-1 uninfected women identified during pregnancy and followed to 9 months postpartum to determine risk and cofactors of HIV-1 incidence. Women who acquire HIV-1 will be compared to women who do not in order to determine the role of genital coinfections, ulcers, delivery practice, lactation, partner characteristics, vaginal flora changes, HSV-2, genital innate immune factors, and systemic immune activation on HIV-1 transmission. In addition, changes in cofactors over the course of pregnancy and postpartum may influence susceptibility to HIV-1. Thus, in a subset of 100 women we will compare genital innate immune factors, and systemic cellular immune activation longitudinally during pregnancy, early postpartum, and later postpartum. These comparisons will provide opportunity to determine patterns of change in the genital tract during this dynamic period of change in women. In quantifying co-infections, mucosal innate immune responses, and systemic cellular immune activation, we will be able to determine interactions between these important determinants in 3 different but inter-related areas (co-infection, mucosal innate milieu, systemic cellular) that affect susceptibility to HIV-1. Project 1 will have scientific links to Project 2 (effects of changes in vaginal flora on HIV-1 transmission), Project 3 (which will involve cytokine profile analyses within women from the Project 1 cohort) and Project 4 (adaptive humoral mucosal responses in HIV-1 uninfected women with HIV-1 infected partners). Because of the complexity of the female genital ecosystem and the variety of factors that could alter susceptibility to HIV-1, each Project will focus on complementary factors that may modify transmission of HIV-1. Together, these will lead to a multi-faceted evaluation of transmission in women in different important groups of women at risk for HIV-1, (pregnant/postpartum, female sex workers, and discordant couples), that conceivably share some cofactors for HIV-1 susceptibility but are distinct in others.