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: 10646200
• 负责人: Phyllis C Tien
• 金额: $ 18.48万
• 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/10646200
• 关键词: Acceleration; Adipose tissue; Affect; African American; Age; Aging; Anti-Retroviral Agents; Antiviral Agents; Award; Behavioral; Behavioral Sciences; 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; Disparity; Drug Exposure; Education; Endocrinology; Epidemiology; Estrogens; Ethnic Origin; Extrahepatic; Fatty Liver; Female; Fibrosis; Functional disorder; Gender; Goals; Gonadal Steroid Hormones; Grant; HIV; HIV Infections; HIV/HCV; Hair; Health; Hepatitis C; Hepatitis C virus; Hepatology; Hispanic; Immune; Immunology; Income; Infection; Inflammation; Inflammatory; Infrastructure; Injury; Injury to Kidney; Integrase; Intestinal permeability; Leadership; Liver; Liver Fibrosis; 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; Recommendation; Regimen; Reporting; Research; Research Personnel; Research Project Grants; Research Support; Risk; Role; Sampling; Site; 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; clinical translation; cohort; elastography; fatty liver disease; food security; gastrointestinal epithelium; gut dysbiosis; gut microbiome; health care availability; health disparity; immune activation; indexing; inhibitor; 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; skills; 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 我是一位接受过传染病 (ID) 和 HIV 流行病学培训的医学教授，他开发了一种 国家认可的临床转化研究计划，重点是了解以下各项之间的关联 HIV 和 HCV 感染引起的脂肪组织变化、代谢和炎症扰动及其影响 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) R01。 建立了约 1500 名 HIV 和/或 HCV 感染女性的纵向多中心队列，以及 两种感染均未感染，以确定 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 和默克研究人员发起的奖项，用于检查 HCV 治愈的影响以及：a) 潜伏的 HIV 储存库、免疫激活和肝纤维化，以及 b) 新颖 接受直接抗病毒药物治疗的患者肾损伤的生物标志物 3) 第二个默克奖； 检查整合酶链抑制剂 (INSTI) 血浆水平与身体成分的关系 变化；4) U01，其核心目标是研究美国男性和女性艾滋病毒的长期进展 来自多中心艾滋病队列研究 (MACS) 和妇女机构间艾滋病毒研究 (WIHS)。 研究资助利用 WIHS 的基础设施，该基础设施于 2019 年成为 MACS-WIHS 联合体 队列研究 (MWCCS) 对于 K24 更新支持的新研究，我将增强我们当前的研究。 女性样本和大约 3000 名 MWCCS 男性将从 2020 年开始接受 FibroScan® 来：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、 居住地区/社区、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影响脂肪变性和纤维化进展；2) 研究 使用客观方法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、血浆和头发 MWCCS 中获得的 INSTI 水平；3) 确定脂肪变性和纤维化如何影响肝外结果 （心脏、神经认知、骨骼）。拟议的研究将扩大我的研究范围并扩展深度。 我的指导计划包括来自一系列新学科的受训者（例如社会行为科学， 内分泌学、药理学和微生物学，以及感染性疾病、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) 的受训者​​，他们可以有效地为艾滋病毒做出贡献 MWCCS 为学员提供了访问丰富的研究平台的便捷途径。 为了在以患者为导向的研究中建立他们的职业生涯，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结构化和可持续的指导计划，以便尽早发展 艾滋病毒研究中的职业中期调查员（特别是 URM 调查员），并确保他们将 最终自己成为熟练的导师。

项目成果

Editorial: Statins and Liver Disease: Is it Time to Recommend Statins to Prevent Liver Disease Progression?

社论：他汀类药物和肝病：是时候推荐他汀类药物来预防肝病进展了吗？

• DOI: 10.1038/ajg.2017.250
• 发表时间: 2017
• 期刊: The American journal of gastroenterology
• 作者: Price,JenniferC;Tien,PhyllisC
• 通讯作者: Tien,PhyllisC