Persistent Functional Immune Defects in Treated HIV Infection

HIV感染治疗后持续存在功能性免疫缺陷

• 批准号: 10593968
• 负责人: PETER W HUNT
• 金额: $ 18.43万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-07 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10593968
• 关键词: AIDS clinical trial group; Acquired Immunodeficiency Syndrome; Address; Adipose tissue; Aging; Anti-Inflammatory Agents; Automobile Driving; Award; Blood Vessels; CD4 Positive T Lymphocytes; CD8-Positive T-Lymphocytes; California; Cardiovascular system; Cells; Cessation of life; Clinical; Cytomegalovirus; Data; Dedications; Defect; Diabetes Mellitus; Disease; Educational workshop; Environment; Epithelial Cells; Etiology; Event; Exhibits; Foundations; Frequencies; Funding; Grant; HIV; HIV Infections; HIV Seropositivity; Heart Diseases; Immune; Immunologic Deficiency Syndromes; Immunologics; Impairment; Individual; Inflammation; Inflammatory; Insulin Resistance; International; Intervention; K-Series Research Career Programs; Laboratories; Life Expectancy; Link; Malignant neoplasm of lung; Mediating; Medicine; Mentored Research Scientist Development Award; Mentors; Mentorship; Mid-Career Clinical Scientist Award (K24); Modernization; Morbidity - disease rate; Non-Insulin-Dependent Diabetes Mellitus; Organ; Pathway interactions; Peer Review; Peptides; Persons; Phase; Physicians; Placebos; Population; Process; Productivity; Publications; Randomized, Controlled Trials; Recovery; Reporting; Research; Research Institute; Research Personnel; Research Training; Risk; Role; San Francisco; Science; Scientist; Secure; Series; Smoking; Substance Use Disorder; T cell infiltration; T-Cell Activation; T-Lymphocyte; TNF gene; Time; Training; Training Activity; Training Programs; Universities; Valganciclovir; Vascular Diseases; Vascular Endothelium; Viral; antiretroviral therapy; base; cardiometabolism; career; career development; co-infection; cohort; collaboratory; disorder risk; gastrointestinal epithelium; high risk; immune activation; improved; indexing; inflammatory marker; inhibitor; interest; lifestyle factors; microbial; mid-career faculty; mortality; multidisciplinary; patient oriented research; programs; skills; skills training; systemic inflammatory response

Project Summary Peter Hunt, MD is an Associate Professor of Medicine in the UCSF Division of Experimental Medicine and an internationally recognized leader in translational Patient-Oriented Research (POR) focused on the causes and consequences of immune activation in treated HIV infection. He is submitting this K24 Mid-Career Development application to afford him protected time to mentor junior investigators, to provide him with dedicated mentorship skills training, and to continue to grow his POR program. The candidate: This proposal will build upon Dr. Hunt's highly productive research program, exemplified by over 200 peer-reviewed publications, a citation h-index of 52, and robust research funding base including three R01 grants and two large projects in the DARE collaboratory and amfAR Institute for HIV Cure Research. He has already demonstrated a strong track record for mentoring, particularly in multidisciplinary team science, including 4 mentees who have successfully applied for K23/K01 awards, and two who have gone on to secure independent R-series grants. He is also the recipient of the 2015 UCSF AIDS Research Institute Award for Mentoring. The environment: He has a rich foundation for supporting his mentees including access to the UCSF SCOPE cohort of >2000 HIV-infected individuals in San Francisco and connections to several other multicenter cohorts (LSOCA, UARTO, CNICS) and research networks including the ACTG, where he served as Chair of the Inflammation and End Organ Disease Committee. Mentorship training: This K24 award will further enhance his mentorship skills through intensive workshops and training modules supported by the UCSF CTSI Mentorship Training Program and the UCSF-GIVI Mentoring the Mentors program. He will also be coached by a robust group of career mentors as he navigates this next phase of his career. Research plan: The overarching hypothesis motivating the research plan is that subclinical immunodeficiency despite treated HIV infection decreases CD8+ T cell-mediated CMV surveillance, which in turn leads to microbial translocation and cardiometabolic complications. The specific aims will: 1) assess the contribution of asymptomatic CMV replication to soluble markers of microbial translocation and vascular dysfunction in treated HIV infection, 2) assess the degree to which treated HIV infection is associated with inflammatory CMV-specific CD8+ T cell infiltration of adipose tissue and insulin resistance, and 3) assess whether maturational defects in CMV-specific CD8+ T cells occur in treated HIV infection. These studies will also serve as ideal POR training platforms for his mentees.

项目概要 Peter Hunt 医学博士是加州大学旧金山分校实验医学部的医学副教授 国际公认的以患者为导向的转化研究 (POR) 领域的领导者，专注于病因和 治疗艾滋病毒感染时免疫激活的后果。他正在提交这份 K24 职业生涯中期报告 开发应用程序，为他提供受保护的时间来指导初级调查员，为他提供 专门的指导技能培训，并继续发展他的 POR 计划。候选人：本提案 将建立在亨特博士高产的研究计划的基础上，该计划以 200 多个经过同行评审的研究项目为例证 出版物、被引 H 指数为 52，以及强大的研究资助基础，包括三项 R01 资助和两项 DARE 合作实验室和 amfAR HIV 治愈研究所的大型项目。他已经 在指导方面表现出良好的记录，特别是在多学科团队科学方面，包括 4 已成功申请 K23/K01 奖项的学员，以及两名已继续获得奖励的学员 独立的 R 系列补助金。他还获得了 2015 年加州大学旧金山分校艾滋病研究所奖 指导。环境：他有丰富的基础来支持他的学员，包括接触 旧金山 UCSF SCOPE 队列中超过 2000 名 HIV 感染者以及与其他几个人的联系 多中心队列（LSOCA、UARTO、CNICS）和研究网络，包括他曾服务过的 ACTG 担任炎症和终末器官疾病委员会主席。导师培训：这个 K24 奖项将 通过由以下机构支持的密集讲习班和培训模块，进一步提高他的指导技能 UCSF CTSI 导师培训计划和 UCSF-GIVI 导师指导计划。他也将是 在他职业生涯的下一阶段中，他受到了一群强大的职业导师的指导。研究计划： 推动该研究计划的首要假设是，尽管接受了治疗，但亚临床免疫缺陷 HIV 感染降低 CD8+ T 细胞介导的 CMV 监测，进而导致微生物易位 和心脏代谢并发症。具体目标将：1）评估无症状 CMV 的贡献 在治疗的 HIV 感染中复制到微生物易位和血管功能障碍的可溶性标记物，2) 评估治疗后的 HIV 感染与炎症性 CMV 特异性 CD8+ T 细胞的相关程度 脂肪组织浸润和胰岛素抵抗，3) 评估 CMV 特异性是否存在成熟缺陷 CD8+ T 细胞出现在治疗的 HIV 感染中。这些研究也将作为理想的 POR 培训平台 他的弟子。