MACS/WIHS -CCS

摘要 感染艾滋病毒的男女中有近一半是生活在南方的少数族裔。HIV感染 尽管有治疗方法，但仍是一个主要的公共卫生问题。这项建议的目的是 通过以下方式增进对艾滋病毒感染后果的认识，重点是艾滋病毒相关的共病 作为多中心艾滋病队列研究(MACS)和妇女研究的临床研究站点(CRS)参加 机构间艾滋病毒研究(WIHS)联合队列研究(MACS/WIHS-CCS)。为了实现这一目标，迈阿密将 提供专业知识，领导CCS统一科学议程的重要组成部分制定方案 和实验室对方案和分研究的支持，以及实施完整的CCS统一科学 议程。为了实现这一目标，我们将招募和跟踪500名感染艾滋病毒或有感染艾滋病毒风险的男性和女性。 我们将招募大约250名反映迈阿密艾滋病毒流行的男性，并跟踪发生性行为的男性 其中男性、双性恋男性和异性恋男性包括黑人或西班牙裔男性代表着 少数人比例。作为目前的南方WIHS网站，我们将继续关注参加 感染艾滋病毒或有感染艾滋病毒风险的WIHS，主要是反映迈阿密艾滋病毒流行的少数群体。使用 随着CCS方案的实施，我们将从社区中再招募100名妇女，以实现以下目标 大约250名妇女。被录取的男性和女性将符合 新注册的MACS/WIHS联盟。迈阿密将继续其强有力的领导，就像我们为 WIHS。作为这项多PI提案的首席PI，Fischl博士是WIHS的副主席，并一直积极 与同事一道，在制定统一的科学议程方面发挥作用，包括具体目标， 访问核心方案的频率以及临床测试、样本采集、调查、评估和 临床测试。迈阿密研究报告将侧重于几个创新领域的议定书和次级研究。探索 艾滋病毒、烟草、兴奋剂使用和抑郁综合征的心血管结局和艾滋病毒进展， 并研究心血管疾病风险和免疫激活的炎性生物标记物，包括性别 不同之处。2.探索口腔、女性生殖器和肠道微生物群对艾滋病毒宿主和 接受抗逆转录病毒治疗。3.评估HIV持续、炎症和感染的并存情况和影响 共病结局的免疫标记物和血浆炎症、淀粉样蛋白病理和先天的标记物 免疫细胞表型对疾病结局的影响。4.检查漏洞和恢复能力的轨迹 以及与艾滋病毒结局和共病的关系，以及心理社会和行为 预测者会影响结果。5.研究心理社会因素和物质之间的生物途径 使用可能会增加心血管疾病，损害神经认知功能，并有助于艾滋病毒的持续存在。5. 利用开发资金支持早期和已建立的研究人员开发创新试点 学习。这些发现将有助于更好地了解艾滋病毒，治疗艾滋病毒，并指导未来的研究。

ABSTRACT Nearly half the men and women with HIV infection are racial/ethnic minorities living in the South. HIV infection remains a major public health problem despite the availability of treatments. The purpose of this proposal is to advance the knowledge of the consequences of HIV infection, with a focus on HIV-related comorbidities, by participating as a Clinical Research Sites (CRS) of the Multi-Center AIDS Cohort Study (MACS) and Women's Interagency HIV Study (WIHS) Combined Cohort Study (MACS/WIHS-CCS). To meet this goal, Miami will provide expertise to lead important components of the CCS unified science agenda with protocol development and laboratory support to protocols and sub studies, as well as implementing the full CCS unified science agenda. To accomplish this, we will enroll and follow 500 men and women with HIV infection or at risk for HIV. We will enroll approximately 250 men reflective of the HIV epidemic in Miami, and follow men who have sex with men, bisexual men, and heterosexual men including men who are black or Hispanic representing a large minority proportion. As a current Southern WIHS site we will continue to follow the 149 women enrolled in WIHS who have HIV infection or at risk for HIV and are largely minority reflecting the Miami HIV epidemic. With availability of the CCS protocol, we will enroll additional 100 women from the community to reach a goal of approximately 250 women. The men and women enrolled will be consistent with protocol requirements of the MACS/WIHS consortium for new enrollments. Miami will continue its strong leadership, as we provided for the WIHS. Dr. Fischl as lead PI for this multiple PI proposal is the Vice Chair of the WIHS and has had an active role, along with colleagues, in the development of the unified science agenda, including the specific aims, frequency of core protocol visits, and timing of clinical tests, specimen collections, surveys, assessments and clinical tests. The Miami CRS will focus on protocols and sub studies in several innovative areas.1. Explore cardiovascular outcomes and HIV progression in the syndemic of HIV, tobacco, stimulant use, and depression, and investigate inflammatory biomarkers of cardiovascular disease risk and immune activation, including sex differences. 2. Explore the effects of the oral, female genital, and gut microbiome on the HIV reservoir and on exposure to antiretroviral therapy. 3. Evaluate comorbidities and effect of HIV persistence, inflammation and immune markers on comorbidity outcomes and plasma markers of inflammation, amyloid pathology and innate immune cell phenotypes on disease outcomes. 4. Examine the trajectories of vulnerabilities and resiliencies and relationship to HIV outcomes and comorbidities, and mechanisms by which psychosocial and behavioral predictors affect outcomes. 5. Examine the biological pathway whereby psychosocial factors and substance use may increase cardiovascular disease, impair neurocognitive function and contribute to HIV persistence. 5. Utilize developmental funds to support early stage and established investigators to develop innovative pilot studies. These findings will lead to improved understanding of HIV, treatment of HIV and guide future research.