SF Bay Area MACS/WIHS Combined Cohort Study

项目摘要 MACS和WIHS是对艾滋病毒感染的长期自然史和治疗史的主要研究， 美国旧金山弗朗西斯科临床研究中心（SF CRS）建议为 MACS/WIHS联合队列研究（MWCCS）科学议程，通过招募和保留 代表本区域艾滋病毒流行病的各种男女群体（即，种族 和种族多样性，护理参与次优）;妇女和社区服务部继续发挥科学领导作用，包括 对与妇女儿童服务中心合作的早期职业调查人员进行强有力的指导; MWCCS研究。按照《妇女、儿童和社区服务计划》，招募和保留感染艾滋病毒和有感染艾滋病毒风险的男性和女性 目标，我们将继续实施多学科招募战略，支持招募符合以下条件的参与者： 代表当地社区的病例和对照。我们将继续提供科学的MWCCS， 通过将MACS和WIHS与数据分析相结合， 协调中心和MWCCS执行委员会，领导新的MWCCS综合科学 工作组，并通过与一个大型的 资深SF CRS调查员核心（5名获得K24奖），他们具有出色的指导技能， 目标是培养新一代熟练的翻译科学家。SF CRS将在以下方面提供领导 对MWCCS科学议程至关重要的几个领域，包括艾滋病毒发病机制， 神经认知障碍和脑结构/功能，基因组学，心脏电生理学，药理学， 信息学和合并症。具体而言，我们建议：1）有助于了解艾滋病毒 通过对外周血、肠组织、宫颈内和外周血中的白细胞群体进行深层表型分析， 2）研究HIV和性腺衰老对神经认知功能缺陷的关系; 3)进行新的心电图研究，以评估亚临床心脏和神经认知损伤， PLWH; 4）利用相关研究更好地了解多种发病率的相互关系（例如，心脏， 外周血管、肝、肾、肺、神经认知、身体功能;和5）铅基因组（例如， 遗传学、表观遗传学、线粒体）发现工作对MWCCS中评价结果的影响。

Project Summary The MACS and WIHS are major studies of the long-term natural and treated history of HIV infection in the U.S. The San Francisco Clinical Research Site (SF CRS) proposes to make vital contributions to the MACS/WIHS Combined Cohort Study (MWCCS) scientific agenda through the recruitment and retention of a diverse group of women and men whom are representative of the HIV epidemic in our region (i.e., racially and ethnically diverse, sub-optimal engagement in care); continued scientific leadership of MWCCS including strong mentoring of early career investigators who work with MWCCS; and consistent participation in MWCCS studies. To enroll and retain both men and women with and at risk for HIV consistent with MWCCS targets, we will continue a strategy of multisource recruiting that supports enrollment of participants who represent cases and controls in the local community. We will continue to provide MWCCS scientific and structural leadership by unifying the MACS and WIHS in collaboration with the data analysis and coordination center and the MWCCS Executive Committee, leading new MWCCS integrated scientific working groups, and supporting early career investigators through the collaborative engagement of a large core of senior SF CRS investigators (five with K24 awards) who have outstanding mentorship skills, with the goal of developing a new generation of skilled translational scientists. The SF CRS will provide leadership in several domains of vital importance to the MWCCS scientific agenda including HIV pathogenesis, neurocognitive impairment and brain structure/function, genomics, cardiac electrophysiology, pharmacology, informatics, and comorbidities. Specifically, we propose to: 1) contribute to the understanding of the HIV reservoir through deep phenotyping of leukocyte populations in peripheral blood, gut tissue, endocervical and seminal cells; 2) examine the relationship of HIV and gonadal aging on deficits in neurocognitive functioning; 3) pursue novel electrocardiographic studies to evaluate subclinical cardiac and neurocognitive injury in PLWH; 4) leverage linked studies to better understand inter-relationships of multiple morbidities (e.g., cardiac, peripheral vascular, hepatic, renal, pulmonary, neurocognitive, physical function; and 5) lead genomic (e.g., genetic, epigenetic, mitochondrial) discovery efforts on the outcomes evaluated in the MWCCS.