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: 10392380
• 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/10392380
• 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; 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; Institutes; 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; Plant Roots; Population; Process; 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 Activation; T-Lymphocyte; TNF gene; Time; Training; Training Activity; Training Programs; Tumor-infiltrating immune cells; 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.

项目摘要 医学博士彼得·亨特（Peter Hunt）是UCSF实验医学部医学副教授， 国际公认的以患者为导向的研究（POR）的领导者着重于原因和 治疗的HIV感染中免疫激活的后果。他正在提交这个K24中期职业者 开发应用程序可以为他提供保护时间，以指导初级调查员 专门的指导技能培训，并继续发展他的POR计划。候选人：此提案 将建立在亨特博士的高产研究计划的基础上，以200多个同行评审说明 出版物，引用H指数为52，以及强大的研究资金基础，其中包括三个R01赠款和两个 DARE合作和AMFAR HIV治疗研究所的大型项目。他已经 在指导方面表现出了良好的记录，尤其是在多学科团队科学中，包括4个 成功申请K23/K01奖的受训者，还有两名继续确保确保的受训者 独立的R系列赠款。他还是2015年UCSF艾滋病研究所奖的获得者 指导。环境：他为支持受训者提供丰富的基础，包括进入 UCSF范围> 2000年的HIV感染者在旧金山和其他几个人的联系 多中心队列（LSOCA，UARTO，CNIC）和包括ACTG在内的研究网络 作为炎症和终结器官疾病委员会主席。指导培训：这个K24奖将 通过强化研讨会和培训模块的支持，进一步提高了他的指导能力 UCSF CTSI指导培训计划和UCSF-GIVI指导指导计划。他也会 在一个强大的职业导师团队中，他在职业生涯的下一个阶段导航。研究计划： 促使研究计划的总体假设是尽管有治疗 HIV感染降低了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。具体目的将：1）评估无症状CMV的贡献 复制对治疗的HIV感染中微生物易位和血管功能障碍的可溶性标记，2） 评估治疗的HIV感染与炎症CMV特异性CD8+ T细胞有关的程度 脂肪组织和胰岛素抵抗的浸润，以及3）评估CMV特异性的成熟缺陷是否存在 CD8+ T细胞发生在治疗的HIV感染中。这些研究还将作为理想的POR培训平台 他的受训者。