Revealing Reservoirs during Rebound (R3)

反弹期间显露储层（R3）

• 批准号: 10223139
• 负责人: David Mitchell Smith
• 金额: $ 250.29万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10223139
• 关键词: AIDS clinical trial group; Acute; Address; Aftercare; Altruism; Anatomy; Anti-Retroviral Agents; Autopsy; Biological; Biological Markers; Blood; Blood Cells; Blood specimen; Brain; CD4 Positive T Lymphocytes; Cell Proliferation; Characteristics; Clinical; Clinical Pathology; Clinical Research; Clinical Virology; Collection; Competence; DNA; Data; Data Set; Development; Early treatment; Ensure; Evolution; Genes; Genetic Drift; HIV; HIV therapy; HLA-DR Antigens; Human body; Immune; Immunologic Markers; Immunologics; Immunology; Individual; Infection; Interruption; Knowledge; Life; Lymphoid Tissue; Measures; Methods; Mission; Modeling; Monitor; Participant; Pathology; Peripheral; Persons; Plasma; Population; Population Sizes; Primary Infection; RNA; Research Methodology; Research Personnel; Research Project Grants; Specimen; T-Cell Activation; T-Lymphocyte; T-Lymphocyte Subsets; Technology; Terminal Disease; Terminally Ill; Testing; Time; Tissue Sample; Tissues; Translational Research; Viral; Virus; analytical method; antiretroviral therapy; biomarker identification; chronic infection; cohort; design; exhaustion; immune activation; innovation; insight; programmed cell death protein 1; programs; quality assurance; reproductive tract; treatment research; viral rebound; virology; virus genetics; volunteer

Abstract Precisely characterizing HIV rebound when antiretroviral therapy (ART) is stopped can offer valuable insights into HIV reservoirs including: • What biological quantities can predict viral rebound dynamics (timing, set-point, slope), • How HIV populates blood cells and anatomic compartments, and • What immune mechanisms are associated with HIV population size and activity, rebound characteristics, and viral population of circulating CD4+ T cells and tissues. A sticky clinical research dilemma is that clinical compromise can occur when ART is stopped. To overcome these dilemmas, the proposed Revealing Reservoirs during Rebound (R3) will: • Analyze currently available clinical, virological and immunological data from 504 well-characterized participants who started ART during acute and early infection, achieved sustained viral suppression, and then interrupted this therapy under monitored studies (Early Treatment Research Project); • Generate new virologic and immunologic data from blood samples collected from 60 participants in the Zurich Primary Infection cohort and 30 participants in the AIDS Clinical Trials Group study “Identification of Biomarkers to Predict Time to Plasma HIV RNA Rebound and Post-Treatment Viral Control during an Intensively Monitored Antiretroviral Pause (IMAP)” (A5345) (Early Treatment Research Project); • Evaluate 20 altruistic HIV-infected people on ART who are terminally-ill and who have voluntarily decided to stop their ART before they die, and who will provide us their blood before and after they stop ART, then their bodies after they die (Late Treatment Research Project); • These large and diverse sets of data, which will require the development of new analytical methods to answer important questions relevant to the HIV cure agenda (Quantitative Methods Research Project). These three Research Projects will be supported by three Cores. • The Administrative Core will ensure effective and efficient management of the program; • The Clinical and Pathology Core will ensure appropriate collection and management of R3 specimens; • The Quality Assurance and Data Core will ensure quality of data that are collected, generated and analyzed across the program. Altogether, the R3 will address these open questions to provide tangible metrics to guide the development of HIV cure strategies and inform the use of biomarkers to ascertain whether or not a cure effort has the intended effect without interrupting ART.

抽象的 当抗逆转录病毒疗法（ART）停止时，精确地表征了HIV反弹可以提供宝贵的见解 进入艾滋病毒水库，包括： •哪些生物学数量可以预测病毒反弹动态（时机，设定点，斜率）， •HIV如何填充血细胞和解剖区室，以及 •哪些免疫机制与艾滋病毒的种群大小和活动，反弹特征有关， 以及循环CD4+ T细胞和组织的病毒种群。 棘手的临床研究困境是，停止艺术时可能会发生临床妥协。克服 这些困境，拟议的反弹期间揭示的水库（R3）将： •分析目前可用的504个临床，病毒学和免疫数据 在急性和早期感染期间开始艺术的参与者，实现了持续的病毒抑制， 然后在受监测的研究（早期治疗研究项目）下中断这种疗法； •从60位参与者收集的血液样本中生成新的病毒学和免疫数据 苏黎世原发性感染队列和艾滋病临床试验小组的30名参与者研究“鉴定 生物标志物可以预测血浆HIV RNA的时间反弹和治疗后病毒控制 对抗逆转录病毒暂停（IMAP）的严格监测”（A5345）（早期治疗研究项目）； •评估20个无私的艾滋病毒感染者，这些人是最终的，自愿决定的 在死亡之前停止艺术，谁会在停止艺术之前和之后向我们提供血液，然后 他们死后的身体（晚期治疗研究项目）； •这些大型和潜水的数据集，这些数据将需要开发新的分析方法 回答与HIV治疗议程相关的重要问题（定量方法研究项目）。 这三个研究项目将得到三个核心的支持。 •行政核心将确保该计划的有效管理； •临床和病理核心将确保对R3标本的适当收集和管理； •质量保证和数据核心将确保收集，生成的数据质量和 在整个程序中进行了分析。 总之，R3将解决这些开放的问题，以提供有形指标，以指导开发 艾滋病毒治愈策略并告知使用生物标志物来确定治疗努力是否已预期 效果而不会中断艺术。