Early Treatment Research Project: Circulating Reservoirs

早期处理研究项目：循环水库

• 批准号: 10223143
• 负责人: CELSA A SPINA
• 金额: $ 33.04万
• 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/10223143
• 关键词: AIDS clinical trial group; Acute; Address; Altruism; Biological Markers; Blood Circulation; Blood specimen; CD4 Positive T Lymphocytes; CD8-Positive T-Lymphocytes; Cells; Chronic; Clinical Virology; Clonal Expansion; Complement; DNA; Data; Diagnosis; Disease remission; Early treatment; Genetic; HIV; HIV Infections; HLA-DR Antigens; Immune; Immune system; Immunologic Factors; Immunologics; Individual; Infection; Interruption; Knowledge; Lead; Life; Measurable; Measures; Memory; Molecular; Monitor; Participant; Peripheral; Persons; Phenotype; Plasma; Population; Population Sizes; Primary Infection; Publishing; RNA; RNA replication; Research Methodology; Research Project Grants; Sampling; Statistical Methods; T memory cell; T-Cell Activation; T-Lymphocyte; T-Lymphocyte Subsets; Time; Variant; Viral; Virus; acute infection; analytical method; antiretroviral therapy; cohort; density; design; exhaustion; genetic variant; inflammatory marker; insight; migration; preservation; programmed cell death protein 1; programs; systemic inflammatory response; treatment research; viral rebound; virology

PROJECT 1. EARLY TREATMENT RESEARCH PROJECT: Circulating Reservoirs While current antiretroviral therapy (ART) can effectively suppress HIV replication and prolong life of infected individuals, the virus persists in a latent state, only to re-emerge when ART is stopped. Without biomarkers that can accurately and consistently predict either time to viral rebound after ART discontinuation, the assessment of HIV remission will require the interruption of ART. Our Revealing Reservoirs during Rebound (R3) program will take the next steps in finding a cure for HIV by understanding how HIV persists in and populates reservoirs throughout the body. Studying people treated early after their infection who have a more preserved immune system offer a unique opportunity to reveal HIV reservoirs, especially reservoirs in circulating CD4+ T cell subsets. The Early Treatment Research Project (RP) will maximize data and samples collected from previous and ongoing ART interruption studies to determine: Aim 1: Virologic and immunologic quantities measured during ART that predict dynamics of viral rebound when ART is stopped; Aim 2: Dynamics of HIV rebounding variants populating CD4+ T cell subsets after ART interruption and decaying in subsets after re-suppression. Aim 3: Immunologic mechanisms associated with HIV persistence during ART and after ART interruption. To address these open questions, this RP will analyze data currently available from over 500 people who started ART during acute and early HIV infection and then interrupted this therapy under monitored conditions. To complement these available data, this RP will also generate and analyze longitudinally collected virologic, genetic and immunologic data from two cohorts (n=90 total) of HIV-infected individuals who also started ART during acute and early infection and then interrupted this therapy. Altogether, this RP will create considerable new knowledge about how HIV resides in circulating reservoirs, but the circulating HIV reservoir is only a part of the total full-body HIV reservoir, therefore, the insights gained in the Early Treatment RP will be investigated in conjunction with the data generated in the Late Treatment RP, which is designed to investigate the full body reservoirs. Data from both of these RP be used to develop and evaluate new analytical methods with the Quantitative Methods RP to more fully understand HIV dynamics throughout the body.

项目1.早期治理研究项目：循环水库 虽然目前的抗逆转录病毒疗法(ART)可以有效地抑制HIV复制，延长感染者的生命 对于个体来说，病毒持续处于潜伏状态，只有在技术停止时才会重新出现。如果没有生物标记物 可以准确和一致地预测ART停用后病毒反弹的任一时间，评估 艾滋病病毒的缓解将需要中断抗逆转录病毒疗法。我们在反弹中揭示的储备库(R3) 该计划将采取下一步，通过了解艾滋病毒如何持续存在和繁殖来找到治愈艾滋病毒的方法 蓄水池遍布全身。研究感染后早期治疗的人，他们有更好的保存 免疫系统提供了一个独特的机会来发现艾滋病毒的宿主，特别是循环中的CD4+T细胞的宿主 细胞子集。早期治疗研究项目(RP)将最大限度地利用从 之前和正在进行的ART中断研究确定： 目标1：在抗逆转录病毒治疗期间测量的病毒学和免疫学参数预测病毒反弹的动态 当艺术停止的时候； 目的2：ART阻断后HIV反弹变异体填充CD4+T细胞亚群的动态变化 在重新抑制后在子集中腐烂。 目的3：抗逆转录病毒治疗期间和阻断抗逆转录病毒治疗后HIV持续存在的免疫学机制。 为了解决这些悬而未决的问题，本RP将分析目前从500多人获得的数据，这些人 在急性和早期艾滋病毒感染期间开始抗逆转录病毒治疗，然后在监测条件下中断这种治疗。 为了补充这些可用的数据，该RP还将生成和分析纵向收集的病毒学， 遗传和免疫学数据来自两组(共90人)同时开始抗逆转录病毒治疗的艾滋病毒感染者。 在急性和早期感染期间，然后中断了这一治疗。 总而言之，这一RP将创造相当多的关于艾滋病毒如何驻留在循环储存库中的新知识，但 循环中的艾滋病毒储存库只是整个全身艾滋病毒储存库的一部分，因此，在 早期治疗RP将结合以下内容进行调查 在后期处理RP中产生的数据， 它是为研究全身储集层而设计的。来自这两个RP的数据都可以用于开发和 用定量方法RP评估新的分析方法，以更全面地了解HIV动态 遍及全身。