Revealing Reservoirs during Rebound (R3)

摘要 当抗逆转录病毒治疗（ART）停止时，精确描述艾滋病毒反弹可以提供有价值的见解 进入艾滋病毒库，包括： ·哪些生物学量可以预测病毒反弹动力学（时间、设定点、斜率）， ·艾滋病毒如何在血细胞和解剖区室中繁殖，以及 ·什么样的免疫机制与艾滋病毒的人口规模和活动，反弹特征， 以及循环CD 4 + T细胞和组织的病毒群体。 一个棘手的临床研究困境是，当ART停止时，可能会发生临床妥协。克服 针对这些难题，建议的回弹期间显示储层（R3）将： ·分析来自504个特征良好的 在急性和早期感染期间开始ART的参与者，实现了持续的病毒抑制， 然后在监测研究中中断这种治疗（早期治疗研究项目）; ·从60名参与者的血液样本中产生新的病毒学和免疫学数据， 苏黎世原发感染队列和30名参与艾滋病临床试验组研究“艾滋病病毒感染的识别”的受试者。 预测治疗期间血浆HIV RNA反弹和治疗后病毒控制时间的生物标志物 强化抗逆转录病毒疗法（IMAP）”（A5345）（早期治疗研究项目）; ·评估20名自愿决定接受抗逆转录病毒治疗的艾滋病毒感染者， 在他们死之前停止他们的ART，谁会在他们停止ART之前和之后为我们提供他们的血液， 他们死后的身体（后期治疗研究项目）; ·这些庞大而多样的数据集，需要开发新的分析方法， 回答有关艾滋病毒治疗议程的重要问题（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。 ·行政核心将确保方案的有效和高效管理; ·临床和病理学核心将确保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、生成和使用的数据的质量。 在整个程序中进行分析。 总而言之，R3将解决这些开放性问题，以提供切实的指标来指导 艾滋病毒治疗策略，并告知生物标志物的使用，以确定治疗工作是否具有预期效果 不影响艺术。

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.