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 我是接受传染病（ID）和艾滋病毒流行病学培训的医学教授，他已经发展 全国认可的临床转化研究计划的重点是了解 HIV和HCV感染，脂肪组织的变化，代谢和炎症扰动及其 对长期器官损伤（肝脏，骨骼和血管）的影响。我目前的支持研究包括：1）A R01 建立了约1500名艾滋病毒和/或HCV感染的纵向多站点队列， 没有感染来确定HIV，HCV和性腺衰老对肝脏脂肪变性和纤维化的影响 使用Fibroscan®进行进展； 2）第二个R01和默克调查员颁发的奖项 HCV治疗的作用： 直接表演抗病毒药物治疗的人的肾脏损伤的生物标志物； 3）第二个默克奖 该研究检查了整合酶链抑制剂（Instis）与身体组成的血浆水平的关联 变化； 4）一个U01的核心目标是研究美国男性和女性艾滋病毒的长期进展 从多中心艾滋病队列研究（MAC）和妇女妇女间艾滋病毒研究（WIHS）。我的 研究赠款利用了WIHS的基础设施，该基础设施在2019年成为Macs-Wihs合并 队列研究（MWCC）。为了获得K24续订的新研究，我将增加当前 〜3000 MWCCS男性的女性样本，她们将从2020年开始接受Fibroscan®的样本：1）检查 与健康相关的差异（社会经济，行为和心理健康状况，即收入，教育， 地区/居住，医疗保健获取，粮食安全和抑郁症），生物性别包括 性腺衰老和祖先信息标记会影响脂肪变性和纤维化进展。 2）调查 与脂肪变性和纤维化进展相关的生物学和免疫途径使用客观 内脏肥胖，性激素水平，肠和口服微生物组分析，血浆和头发的测量 在MWCC中获得的Insti水平； 3）确定脂肪变性和纤维化如何影响外脑外结局 （心脏，神经认知，骨骼）。拟议的研究将扩大我的研究组合并扩展深度 在我的心理计划中，包括一系列新学科的Mentores（例如，社会行为科学， 内分泌学，药理学和微生物学，除了ID，肝病学和心脏病学的受训者）， 以及可以有效地为艾滋病毒做出贡献的代表性不足的少数民族（URM）群体的梅内斯 当今社区最有风险。 MWCC为月经提供了可以访问丰富的研究平台的月经 在以患者为导向的研究中建立职业。我计划在专业和多样性方面进行其他培训 领导以及如何建立一个结构化和可持续的心理计划，以便尽早发展 艾滋病毒研究中的职业中期调查员（尤其是URM调查人员），并确保他们将 最终成为熟练的导师自己。