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）：我是一名接受过传染病和 HIV 流行病学培训的内科医生，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 (UCSF) 以来，我制定了一项全国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以及代谢和炎症扰动之间的关系，包括肝脂肪变性（或脂肪肝病）。我目前支持的研究包括：1) R01 建立了一个主要由 300 名 HIV 和 HCV 单一感染、HIV/HCV 双重感染以及两者均未感染的男性组成的队列，以确定内脏肥胖、HIV、HCV 及其代谢的影响 以及炎症对脂肪肝疾病的影响（VAHH 研究）； 2) U01 在一个大型前瞻性女性艾滋病毒感染者和有感染艾滋病毒风险的人群中进行（女性机构间艾滋病毒研究 [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对器官的影响受伤。我还可以获得 HIV 感染中脂肪重新分布和代谢变化研究 (FRAM) 的数据。在此框架内，我建议将我的研究议程扩展到：（1）研究 HIV、HCV 及其代谢和炎症后果对长期结果的贡献，包括使用新型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关系的性别差异（通过汇集从 WIHS 女性以及 VAHH 和 FRAM 男性和女性收集的详细结果数据）以及更年期过渡如何进一步发展与男性相比，改变女性的这些关系； (3) 利用这些结果来定义性别特异性机制，使干预研究能够在这些结果的发病机制中考虑到性别影响。 HIV 感染者和 HCV 感染者。可以访问这三个队列中广泛严格收集的测量结果（包括通过超声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颈动脉内膜测量）通过超声波测量介质厚度），我建议将我的指导计划扩大到对艾滋病毒和丙肝病毒感染感兴趣的受训者，他们来自多个学科，包括传染病、肝病学、内分泌学和新陈代谢、心脏病学和放射学。从传染病以外的学科引进学员的能力将进一步丰富我的研究项目。我还计划寻求专业领导力以及如何建立结构化和可持续的指导计划方面的额外培训，以培养艾滋病毒和丙型肝炎研究领域的下一代临床研究人员，并确保他们最终成为熟练的导师。