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

HIV、HCV 和性别对肝脏、骨骼和血管健康的影响

• 批准号: 8875588
• 负责人: Phyllis C Tien
• 金额: $ 13.38万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-15 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8875588
• 关键词: Accounting; Adipose tissue; Age; Ankle; Attenuated; Behavioral Mechanisms; Blood Vessels; Bone Density; California; Cardiology; Central obesity; Chronic; Clinical; Clinical Investigator; Collaborations; Communicable Diseases; Data; Development; Discipline; Disease Progression; Dual-Energy X-Ray Absorptiometry; Endocrinology; Ensure; Epidemiology; Estrogens; Faculty; Fatty Liver; Fatty acid glycerol esters; Fibrosis; Gender; General Population; Goals; Grant; HIV; HIV Infections; Health; Hepatitis C; Hepatitis C virus; Hepatology; Histologic; Hormones; Immune; Infection; Inflammation; Inflammatory; Injury; Internist; Leadership; Liver; Liver Fibrosis; Liver diseases; Magnetic Resonance Imaging; Measurement; Measures; Mediating; Menopause; Mentors; Metabolic; Morbidity - disease rate; Obesity; Organ; Osteoporosis; Outcome; Ovarian; Pathogenesis; Persons; Population; Radiology Specialty; Relative (related person); Research; Research Personnel; Research Support; Risk; San Francisco; Scanning; Serum Markers; Sex Characteristics; Structure; Techniques; Training; Translational Research; Ultrasonography; Universities; Up-Regulation; Vascular Diseases; Visceral; Woman; base; bone; bone loss; burden of illness; cardiovascular risk factor; career; co-infection; cohort; cytokine; elastography; fibrogenesis; immune activation; indexing; inflammatory marker; interest; intimal medial thickening; men; mortality; next generation; novel; programs; prospective; protective effect; sex

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.

描述（由申请人提供）：我是接受传染病和艾滋病毒流行病学培训的内科医生，其研究侧重于HIV和HCV感染。自2000年加入加州大学旧金山大学（UCSF）的教职员工以来，我开发了一项全国认可的临床翻译研究计划，重点是了解HIV感染和HCV感染与脂肪组织的变化，以及代谢性和炎症性的伴随，以及包括肝静脉炎（包括肝静原病）（或脂肪症（或脂肪症）（或脂肪症）。我目前支持的研究包括：1）一个R01，该R01主要建立了一组艾滋病毒和HCV单感染，HIV/HCV共感染的人群，而既没有感染的人都可以确定内脏肥胖，HIV，HIV，HCV及其代谢的影响 和对脂肪肝病的炎症后果（VAHH研究）； 2）在大量前瞻性妇女中，有一个U01有艾滋病毒妇女的妇女（妇女妇女间艾滋病毒研究[WIHS]），其核心目标是确定艾滋病毒的贡献，宿主免疫机制，行为和心血管危险因素对器官损伤的贡献。我也可以使用来自HIV感染（FRAM）的脂肪再分配和代谢变化的研究。在此框架内，我建议将研究议程扩展到：（1）研究HIV，HCV及其代谢和炎症后果对长期结局的贡献，包括使用新型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局的性别差异（通过汇总从WIHS女性，VAHH和FRAM男性和女性收集的详细结果数据）以及与男性相比，女性中的这些关系可能会进一步改变这些关系； （3）使用结果来定义性别特异性机制，这些机制将实现介入的研究，以考虑到这些结果在这些结果的发病机理中的性影响 感染HIV的人和HCV感染者。随着从这三个队列中获得广泛收集的测量范围（包括通过超声基于超声的瞬态弹性图测量肝纤维化，通过MRI测量肝脂肪变性和内脏脂肪组织，双能矿物质密度，通过双能量通过X射线X射线吸收量尺寸扫描和CarotIt Intima Media Intose to Intersose to Intersose to Intersose Intimant intimage intima formose Intim intima来自多种学科的HCV感染，包括传染病，肝病学，内分泌学和代谢，心脏病学和放射学。从传染病之外的学科中吸引受训者的能力将进一步丰富我的研究计划。我计划还寻求有关专业领导力的额外培训，以及如何建立一个结构化和可持续的指导计划，以发展下一代HIV和HCV研究中的临床研究人员，并确保他们最终将自己成为熟练的导师。