HIV, HCV, and gender effects on Liver, Bone, and Vascular Health

描述（由申请人提供）：我是一名内科医生，接受过传染病和HIV流行病学培训，其研究重点是HIV和HCV感染。自2000年加入加州大学旧金山分校弗朗西斯科（UCSF）以来，我已经开发了一个国家认可的临床转化研究计划，重点是了解HIV感染和HCV感染与脂肪组织变化，代谢和炎症扰动，包括肝脂肪变性（或脂肪肝疾病）的关联。我目前支持的研究包括：1）R 01，建立了一个主要由300名HIV和HCV单一感染、HIV/HCV合并感染和两种感染都没有的男性组成的队列，以确定内脏肥胖、HIV、HCV及其代谢的影响。 和炎症对脂肪肝疾病的影响（VAHH研究）;和2）U 01在一个大型的前瞻性队列的妇女与艾滋病毒和风险（妇女的跨机构艾滋病毒研究[WIHS]），其核心目标是确定艾滋病毒，宿主免疫机制，行为和心血管危险因素的贡献器官损伤。在此框架内，我建议将我的研究议程扩展到：（1）调查HIV、HCV及其代谢和炎症后果对长期结果的贡献，包括使用新的非侵入性技术测量的肝病进展，以及骨质疏松症和血管疾病;（2）确定HIV、HCV及其代谢和炎症后果与长期结果之间的关系的性别差异（通过汇总从WIHS女性和VAHH以及弗拉姆男性和女性收集的详细结局数据）以及与男性相比，绝经过渡如何进一步改变女性中的这些关系;和（3）使用结果来定义性别特异性机制，这将使干预性研究能够在这些结果的发病机制中考虑性别效应， HIV感染者和HCV感染者。通过访问从这三个队列中严格收集的广泛测量数据，（包括通过基于超声的瞬时弹性成像测量肝纤维化，通过MRI测量肝脂肪变性和内脏脂肪组织，通过双能X射线吸收测量扫描测量骨矿物质密度，以及通过超声测量颈动脉内膜中层厚度），我建议将我的指导计划扩展到对来自多个学科的HIV和HCV感染感兴趣的学员，包括传染病，肝病学，内分泌学和代谢学，心脏病学和放射学。能够从传染病以外的学科引进学员将进一步丰富我的研究计划。我还计划寻求专业领导方面的额外培训，以及如何建立一个结构化和可持续的指导计划，以培养下一代HIV和HCV研究的临床研究人员，并确保他们最终成为熟练的导师。

DESCRIPTION (provided by applicant): I am an internist trained in infectious disease and HIV epidemiology, whose research is focused on HIV and HCV infections. Since joining the faculty at the University of California, San Francisco (UCSF) in 2000, I have developed a nationally recognized clinical translational research program focused on understanding the associations of HIV infection and HCV infection with adipose tissue changes, and metabolic and inflammatory perturbations, including hepatic steatosis (or fatty liver disease). My currently supported research includes: 1) an R01 that establishes a cohort of mainly 300 men with HIV and HCV monoinfection, HIV/HCV coinfection and those with neither infection to determine the effects of visceral adiposity, HIV, HCV and their metabolic and inflammatory consequences on fatty liver disease (VAHH Study); and 2) a U01 in a large prospective cohort of women with and at risk for HIV (Women's Interagency HIV Study [WIHS]) that has a core goal to determine the contribution of HIV, host immune mechanisms, behavioral and cardiovascular risk factors to organ injury. Data from the Study of Fat Redistribution and Metabolic Change in HIV infection (FRAM) also is available to me. Within this framework, I propose to expand my research agenda to: (1) investigate the contribution of HIV, HCV, and their metabolic and inflammatory consequences to long term outcomes including liver disease progression measured using novel non-invasive techniques, as well as osteoporosis and vascular disease; (2) determine sex differences in the association of HIV, HCV, and their metabolic and inflammatory consequences with long term outcomes (by pooling the detailed outcomes data collected from WIHS women and VAHH and FRAM men and women) and how the menopausal transition may further alter these relationships in women compared to men; and (3) use the results to define sex-specific mechanisms that will enable interventional studies that take into account sex effects in the pathogenesis of these outcomes in HIV-infected and HCV-infected persons. With access to the broad range of rigorously collected measurements from these three cohorts (including measurement of liver fibrosis by ultrasound based transient elastography, hepatic steatosis and visceral adipose tissue by MRI, bone mineral density by Dual Energy X-Ray Absorptiometry scans, and carotid intima media thickness by ultrasound), I propose to expand my mentoring program to mentees with an interest in HIV and HCV infections from a multitude of disciplines including infectious diseases, hepatology, endocrinology and metabolism, cardiology, and radiology. The ability to bring in mentees from disciplines outside of infectious diseases will further enrich my research program. I plan to also seek additional training in professional leadership and how to build a structured and sustainable mentoring program in order to develop the next generation of clinical investigators in HIV and HCV research, and to ensure that they will ultimately become skilled mentors themselves.