Quantitative Methods Research Project

定量方法研究项目

• 批准号: 10223145
• 负责人: VICTOR GERARD DEGRUTTOLA
• 金额: $ 48.25万
• 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/10223145
• 关键词: Anatomy; Autopsy; Biological; Biological Markers; Biological Response Modifier Therapy; Blood; Brain; CD4 Positive T Lymphocytes; Cells; Clinical; DNA; Data; Development; Diagnostic; Distributional Activity; Early treatment; Future; Generations; Genital; Genitalia; Gut associated lymphoid tissue; HIV; Immune; Immune response; Immunologics; Individual; Infection; Interruption; Lymphoid Tissue; Measurement; Measures; Medicine; Methods; Modality; Modeling; New Agents; Outcome Measure; Participant; Persons; Population; Population Dynamics; Population Heterogeneity; Population Process; Population Sizes; Process; RNA; Research; Research Methodology; Research Project Grants; Resources; Sampling; T-Lymphocyte; T-Lymphocyte Subsets; Talents; Technology; Terminally Ill; Time; Tissues; Viral; Viremia; antiretroviral therapy; deep sequencing; exhaustion; immune activation; inducible gene expression; insight; large datasets; new technology; novel strategies; programs; treatment research; viral rebound; virology

Project 3 - QUANTITATIVE METHODS RESEARCH PROJECT - Abstract Over the past three decades, there have been great advances in HIV research, especially in diagnostics and treatment. Curing HIV will require further advances, particularly in the development of new agents and methods for evaluating incremental improvements in their contribution to cure. Our proposed Revealing Reservoirs during Rebound (R3) program will use a large battery of new technologies to investigate how HIV persists in and populates reservoirs throughout the body. Such new insights will be crucial in developing strategies aimed at curing HIV. To make maximal use of existing and newly generated data requires parallel advances in quantitative methods; hence, we propose a Quantitative Methods Research Project (RP). This RP will maximize the utility of data and samples collected in the overall program through the development of novel approaches for their analysis. The aims of our Quantitative Methods RP include: Aim 1: Discover biomarkers that can predict viral rebound when antiretroviral therapy (ART) is stopped to help guide future curative strategies. Aim 2: Precisely characterize HIV populations in T cell subsets and throughout the body and the impact of treatment interruption and re-initiation on these viral populations. Aim 3: Determine immune mechanisms by which HIV populations persist during ART by measuring biological quantities associated with viral rebound dynamics after stopping ART, and HIV population dynamics in cellular subsets and anatomic compartments. Aim 4: Create a global host model that uses mechanistic and empiric modeling methods to integrate our observations from viral rebound dynamics, HIV population of T cell subsets and tissues, and immunologic and virologic quantities to better understand the HIV in the body and the factors that sustain HIV persistence during ART and contribute to viral rebound when ART is stopped. The successful completion of these aims will provide the analytical framework to better understand the mechanistic underpinning of how HIV persists in the setting of ART, and what factors may be attractive targets to disrupt this viral persistence.

项目 3 - 定量方法研究项目 - 摘要 过去三十年来，艾滋病毒研究取得了巨大进展，特别是在诊断方面 和治疗。治愈艾滋病毒需要进一步的进展，特别是在开发新药物和 评估其对治愈贡献的渐进改进的方法。 我们提出的反弹期间揭示储层（R3）计划将使用大量新的 研究艾滋病毒如何在全身的储存库中持续存在和繁殖的技术。这么新的 洞察力对于制定治愈艾滋病毒的战略至关重要。最大限度地利用现有的和 新生成的数据需要定量方法的并行进步；因此，我们提出一个 定量方法研究项目（RP）。该RP将最大化数据和样本的效用 通过开发新的分析方法在整个计划中收集。目标 我们的定量方法 RP 包括： 目标 1：发现可以预测停止抗逆转录病毒治疗 (ART) 时病毒反弹的生物标志物 帮助指导未来的治疗策略。 目标 2：准确描述 T 细胞亚群和整个身体中的 HIV 群体特征以及其影响 对这些病毒群体的治疗中断和重新开始。 目标 3：通过测量来确定 HIV 群体在 ART 期间持续存在的免疫机制 停止 ART 后与病毒反弹动态相关的生物量和 HIV 群体 细胞亚群和解剖区室的动态。 目标 4：创建一个全局宿主模型，使用机械和经验建模方法来集成我们的 病毒反弹动力学、T 细胞亚群和组织的 HIV 群体以及免疫学观察 和病毒学数量，以更好地了解体内的艾滋病毒以及维持艾滋病毒的因素 ART 期间持续存在，并在 ART 停止时导致病毒反弹。 这些目标的成功完成将为更好地理解 HIV 在 ART 环境中持续存在的机制基础，以及哪些因素可能有吸引力 目标是破坏这种病毒的持久性。