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: 10220710
• 负责人: Phyllis C Tien
• 金额: $ 13.23万
• 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 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10220710
• 关键词: Adipose tissue; Affect; African American; Age; Aging; Anti-Retroviral Agents; Antiviral Agents; Award; Behavioral; Biological; Biological Markers; Biological Process; Blood Vessels; Body Composition; Bone Injury; Cardiac; Cardiology; Cardiovascular system; Central obesity; Clinical; Clinical Investigator; Cohort Studies; Collaborations; Communicable Diseases; Communities; Data; Discipline; Disease Progression; Drug Exposure; Education; Endocrinology; Ensure; Epidemiology; Estrogens; Ethnic Origin; Extrahepatic; Fatty Liver; Female; Fibrosis; Functional disorder; Gender; Goals; Gonadal Steroid Hormones; Grant; HIV; HIV Infections; Hair; Health; Hepatitis C; Hepatitis C virus; Hepatology; Hispanics; Immune; Immunology; Income; Infection; Inflammation; Inflammatory; Infrastructure; Injury; Injury to Kidney; Integrase; Intestinal permeability; Leadership; Liver; Liver Fibrosis; Liver diseases; Longitudinal Studies; Measurement; Medicine; Menopause; Mental Depression; Mental Health; Mentors; Mentorship; Metabolic; Microbiology; Minority Groups; Morbidity - disease rate; Neighborhoods; Neurocognition; Neurocognitive; Neuropsychology; Obesity; Outcome; Pathogenesis; Pathway interactions; Perimenopause; Persons; Pharmacology; Plasma; Play; Race; Regimen; Reporting; Research; Research Personnel; Research Project Grants; Research Support; Risk; Role; Sampling; Science; Social Behavior; Structure; Tenofovir; The Multicenter AIDS Cohort Study; Training; Underrepresented Minority; Viral; Visceral; Weight Gain; Woman; Women' s Interagency HIV Study; Work; behavioral health; biological sex; bone; career; cohort; elastography; food security; gastrointestinal epithelium; gut dysbiosis; gut microbiome; health care availability; health disparity; immune activation; indexing; inhibitor/antagonist; kidney fibrosis; latent HIV reservoir; liver injury; men; microbial; microbiome analysis; minority investigator; mortality; next generation; non-alcoholic fatty liver disease; novel marker; optimism; oral microbiome; organ injury; patient oriented research; professor; programs; residence; socioeconomics; systemic inflammatory response; translational research program; vibration; waist circumference

PROJECT ABSTRACT I am a Professor of Medicine trained in infectious diseases (ID) and HIV epidemiology, who has developed a nationally recognized clinical translational research program focused on understanding the associations of HIV and HCV infection with adipose tissue changes, and metabolic and inflammatory perturbations, and their effects on long-term organ injury (liver, bone, and vascular). My current supported research includes: 1) a R01 that establishes a longitudinal multisite cohort of ~1500 women with HIV and/or HCV infection, and those with neither infection to determine the effects of HIV, HCV, and gonadal aging on liver steatosis and fibrosis progression using FibroScan®; 2) a second R01 and a Merck investigator-initiated award that examines the effects of HCV cure and: a) latent HIV reservoirs, immune activation, and liver fibrosis and b) novel biomarkers of kidney injury in persons treated with direct acting antiviral agents; 3) a second Merck award that examines the association of plasma levels of integrase strand inhibitors (INSTIs) with body composition changes; and 4) a U01 whose core goal is to study the long-term progression of HIV in U.S. men and women from the Multicenter AIDS Cohort Study (MACS) and the Women’s Interagency HIV Study (WIHS). My research grants leverage the infrastructure of the WIHS, which in 2019 became the MACS-WIHS Combined Cohort Study (MWCCS). For the new research to be supported by the K24 renewal, I will augment our current sample of women with ~3000 MWCCS men who will undergo FibroScan® beginning in 2020 to: 1) examine how health-related disparities (socioeconomic, behavioral and mental health conditions, i.e. income, education, region/neighborhood of residence, healthcare access, food security, and depression), biologic sex including gonadal aging, and ancestry informative markers influence steatosis and fibrosis progression; 2) investigate the biologic and immune pathways associated with steatosis and fibrosis progression using objective measurement of visceral adiposity, sex hormone levels, gut and oral microbiome analysis, plasma and hair INSTI levels obtained in the MWCCS; 3) determine how steatosis and fibrosis affects extrahepatic outcomes (cardiac, neurocognition, bone). The proposed studies will expand my research portfolio and extend the depth of my mentoring program to include mentees from an array of new disciplines (e.g. socio-behavioral sciences, endocrinology, pharmacology, and microbiology, in addition to mentees in ID, hepatology, and cardiology), and mentees from underrepresented minority (URM) groups who can effectively contribute to the HIV communities most at risk today. The MWCCS provides mentees with ready access to a rich research platform to build their careers in patient-oriented research. I plan additional training in professional and diversity leadership and how to build a structured and sustainable mentoring program in order to develop early and mid-career investigators (especially URM investigators) in HIV research, and to ensure that they will ultimately become skilled mentors themselves.

项目摘要 我是一名接受过传染病和艾滋病流行病学培训的医学教授， 国家认可的临床转化研究计划，专注于了解 HIV和HCV感染伴脂肪组织变化、代谢和炎症紊乱，以及它们的 对长期器官损伤（肝脏、骨骼和血管）的影响。我目前支持的研究包括：1）R 01 该研究建立了一个由约1500名HIV和/或HCV感染妇女组成的纵向多地点队列， 两种感染都没有，以确定HIV、HCV和性腺老化对肝脂肪变性和纤维化的影响。 使用FibroScan®的进展; 2）第二个R 01和默克制药公司发起的奖项， HCV治愈的效果和：a）潜伏的HIV储库、免疫激活和肝纤维化，以及B）新的 直接作用抗病毒剂治疗患者肾损伤的生物标志物; 3）第二个默克奖 研究整合酶链抑制剂（INSTIs）的血浆水平与身体组成的关系 变化;以及4）U 01，其核心目标是研究美国男性和女性艾滋病毒的长期进展 多中心艾滋病队列研究（MACS）和妇女跨机构艾滋病研究（WIHS）。我 研究赠款利用WIHS的基础设施，该基础设施在2019年成为MACS-WIHS组合 队列研究（MWCCS）。为了让K24更新支持新的研究，我将增加我们目前的 将于2020年开始接受FibroScan®的约3000 MWCCS男性女性样本：1）检查 与健康有关的差异（社会经济、行为和心理健康状况，即收入、教育、 区域/居住区，医疗保健服务，食品安全和抑郁症），生物性别，包括 性腺老化和祖先信息标记物影响脂肪变性和纤维化进展; 2）研究 与脂肪变性和纤维化进展相关的生物和免疫途径， 内脏脂肪测量、性激素水平、肠道和口腔微生物组分析、血浆和毛发 在MWCCS中获得的CIMI水平; 3）确定脂肪变性和纤维化如何影响肝外结局 （心脏、神经认知、骨骼）。拟议的研究将扩大我的研究组合，并扩大深度 我的指导计划包括来自一系列新学科的学员（例如社会行为科学， 内分泌学、药理学和微生物学，以及ID、肝病学和心脏病学的学员）， 以及来自代表性不足的少数群体（URM）的学员，他们可以有效地为艾滋病毒做出贡献。 今天最危险的社区。MWCCS为学员提供了一个丰富的研究平台 在以病人为导向的研究中建立自己的职业生涯。我计划在专业和多样性方面进行额外的培训 领导力以及如何建立一个结构化且可持续的指导计划，以便尽早发展并 艾滋病毒研究的职业中期研究人员（特别是URM研究人员），并确保他们 最终成为自己的导师。