HIV 临床试验中的分析治疗中断：统计和研究设计考虑。
Analytical Treatment Interruption in HIV Trials: Statistical and Study Design Considerations.
机构信息
Center for Biostatistics in AIDS Research, Department of Biostatistics, Harvard T.H. Chan School of Public Health, 651 Huntington Avenue, Boston, MA, 02115, USA.
出版信息
Curr HIV/AIDS Rep. 2021 Oct;18(5):475-482. doi: 10.1007/s11904-021-00569-8. Epub 2021 Jul 2.
Abstract
PURPOSE OF REVIEW
Analytical treatment interruption (ATI) remains an essential component in clinical studies investigating novel agents or combination treatment strategies aiming to induce HIV treatment-free remission or long-term viral control. We provide an overview on key study design aspects of ATI trials from the perspective of statisticians.
RECENT FINDINGS
ATI trial designs have evolved towards shorter treatment interruption phases and more frequent viral load monitoring aiming to reduce prolonged viremia risks. Criteria for ART resumption have evolved as well. Common outcome measures in modern ATI trials include time to viral rebound, viral control, and viral set point. Design of the ATI component in HIV clinical trials is driven by the scientific question and the mechanism of action of the intervention being investigated.
摘要
目的综述
分析性治疗中断（ATI）仍然是临床研究的一个重要组成部分，这些研究旨在探索新型药物或联合治疗策略，以诱导 HIV 治疗无缓解或长期病毒控制。我们从统计学家的角度提供了关于 ATI 试验关键研究设计方面的概述。
最近的发现
ATI 试验设计已经朝着更短的治疗中断阶段和更频繁的病毒载量监测方向发展，旨在降低长期病毒血症的风险。ART 恢复的标准也在不断发展。现代 ATI 试验中的常见结果测量包括病毒反弹时间、病毒控制和病毒设定点。HIV 临床试验中 ATI 部分的设计取决于正在研究的干预措施的科学问题和作用机制。
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2
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3
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