Revealing Reservoirs during Rebound (R3)

摘要 准确地描述抗逆转录病毒治疗(ART)停止时艾滋病毒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)， ·艾滋病毒如何填充血细胞和解剖隔间，以及 ·哪些免疫机制与艾滋病毒种群规模和活动、反弹特征、 以及循环中的CD4T细胞和组织中的病毒群。 一个棘手的临床研究困境是，当ART停止时，可能会出现临床妥协。要克服 这些困境，建议揭示的反弹期间的水库(R3)将： ·分析504个特征良好的患者的现有临床、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，以及 然后在监测研究(早期治疗研究项目)下中断该治疗； ·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艾滋病临床试验小组研究的30名参与者 预测艾滋病患者血浆HIV-RNA反弹和治疗后病毒控制时间的生物标志物 密集监测抗逆转录病毒暂停(IMAP)“(A5345)(早期治疗研究项目)； ·在抗逆转录病毒疗法上评估20名身患绝症并自愿做出决定的无私艾滋病毒感染者 在他们死前停止他们的艺术，那么，在他们停止艺术之前和之后，谁会为我们提供他们的血液 他们死后的遗体(晚期治疗研究项目)； ·这些庞大而多样的数据集，将需要开发新的分析方法来 回答与艾滋病毒治疗议程(定量方法研究项目)相关的重要问题。 这三个研究项目将得到三个核心的支持。 ·行政核心将确保有效和高效地管理方案； ·临床和病理核心将确保适当收集和管理R3标本； ·质量保证和数据核心将确保收集、生成和 在整个项目中进行了分析。 总而言之，R3将解决这些公开问题，以提供切实的指标来指导 艾滋病毒治疗策略和生物标志物的使用，以确定治疗努力是否有预期的 在不中断艺术的情况下产生效果。

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.