Revealing Reservoirs during Rebound (R3)

摘要 准确描述停止抗逆转录病毒治疗 (ART) 时 HIV 反弹的特征可以提供有价值的见解 进入艾滋病毒储存库，包括： • 哪些生物量可以预测病毒反弹动态（时间、设定点、斜率）、 • HIV 如何在血细胞和解剖区中繁殖，以及 • 哪些免疫机制与 HIV 群体规模和活动、反弹特征、 以及循环 CD4 T 细胞和组织的病毒群体。 临床研究的一个棘手困境是，当 ART 停止时，可能会出现临床妥协。克服 面对这些困境，拟议的反弹期间揭示储层（R3）将： • 分析来自 504 个特征明确的当前可用的临床、病毒学和免疫学数据 在急性和早期感染期间开始抗逆转录病毒治疗的参与者实现了持续的病毒抑制，并且 然后根据监测研究（早期治疗研究项目）中断该治疗； • 从 60 名参与者收集的血液样本中生成新的病毒学和免疫学数据 苏黎世原发性感染队列和艾滋病临床试验组研究“识别 生物标志物可预测血浆 HIV RNA 反弹时间和治疗后病毒控制 强化监测抗逆转录病毒暂停 (IMAP)”(A5345)（早期治疗研究项目）； • 评估 20 名接受 ART 的无私 HIV 感染者，他们身患绝症并自愿决定接受 ART 在他们死前停止他们的 ART，谁会在他们停止 ART 之前和之后向我们提供他们的血液，然后 他们死后的尸体（后期治疗研究项目）； • 这些庞大且多样化的数据集需要开发新的分析方法来 回答与艾滋病毒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、生成和处理的数据的质量。 整个程序进行了分析。 总而言之，R3 将解决这些悬而未决的问题，以提供切实的指标来指导开发 HIV 治疗策略并告知生物标志物的使用，以确定治疗工作是否达到预期目的 不中断 ART 的效果。

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.