Considerations in the rationale, design and methods of the Strategic Timing of AntiRetroviral Treatment (START) study.
Considerations in the rationale, design and methods of the Strategic Timing of AntiRetroviral Treatment (START) study.
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DOI：
10.1177/1740774512440342
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
INSIGHT START Study Group
中科院分区：
文献类型：
--
作者：
Babiker AG;Emery S;Fätkenheuer G;Gordin FM;Grund B;Lundgren JD;Neaton JD;Pett SL;Phillips A;Touloumi G;Vjechaj MJ;INSIGHT START Study Group
未经治疗的人类免疫缺陷病毒（HIV）感染的特征是CD 4 + T淋巴细胞（CD 4）计数的进行性耗竭，导致机会性疾病（获得性免疫缺陷综合征（AIDS））的发展，最近的数据表明，HIV还与严重非AIDS（SNA）疾病（包括心血管、肾脏和肝脏疾病以及非AIDS定义的癌症）的风险增加有关。虽然联合抗逆转录病毒治疗（ART）已导致艾滋病毒感染者的发病率和死亡率大幅下降，但用现有药物根除病毒是不可行的。对于无症状HIV感染者开始ART的最佳时间是有争议的，并且仍然是HIV感染者临床管理中未回答的关键问题之一。在这篇文章中，我们概述了抗逆转录病毒治疗的战略时机（START）研究的基本原理和方法，这是一项正在进行的多中心国际试验，旨在评估比目前更早开始ART的风险和益处。我们还描述了一些在设计和实施研究中遇到的挑战，以及如何解决这些挑战。总共有4000名HIV-1感染、ART初治且CD 4计数> 500个细胞/μL的研究参与者将以1：1的比例随机分配，立即开始ART（早期ART）或推迟治疗，直至CD 4计数<350个细胞/ μL（推迟ART），并随访至少3年。主要结果是到艾滋病、SNA或死亡的时间。该研究有一个试点阶段，以确定累积的可行性，第一年至少招募900名参与者。研究设计和实施中遇到的挑战包括研究人群中主要终点（SNA）主要成分风险的数据有限，试验阶段顺利进行时治疗指南的变化，以及在具有不同监管要求的地理范围广泛的人群中进行试验的复杂性。随着试点阶段的成功完成，来自23个国家100个地点的1000多名参与者已经注册。该研究将扩展至36个国家的237个研究中心，以达到4000例受试者的目标招募。START正在解决ART临床管理中最重要的问题之一。随机化为进行几项子研究提供了一个平台，旨在增加我们对HIV疾病和抗逆转录病毒治疗效果的理解，超越试验的主要问题。从其设计和实施中吸取的经验教训有望对未来公共资助的国际审判有所帮助。
Untreated human immunodeficiency virus (HIV) infection is characterized by progressive depletion of CD4+ T lymphocyte (CD4) count leading to the development of opportunistic diseases (acquired immunodeficiency syndrome (AIDS)), and more recent data suggest that HIV is also associated with an increased risk of serious non-AIDS (SNA) diseases including cardiovascular, renal, and liver diseases and non-AIDS-defining cancers. Although combination antiretroviral treatment (ART) has resulted in a substantial decrease in morbidity and mortality in persons with HIV infection, viral eradication is not feasible with currently available drugs. The optimal time to start ART for asymptomatic HIV infection is controversial and remains one of the key unanswered questions in the clinical management of HIV-infected individuals. In this article, we outline the rationale and methods of the Strategic Timing of AntiRetroviral Treatment (START) study, an ongoing multicenter international trial designed to assess the risks and benefits of initiating ART earlier than is currently practiced. We also describe some of the challenges encountered in the design and implementation of the study and how these challenges were addressed. A total of 4000 study participants who are HIV type 1 (HIV-1) infected, ART naïve with CD4 count > 500 cells/μL are to be randomly allocated in a 1:1 ratio to start ART immediately (early ART) or defer treatment until CD4 count is <350 cells/ μL (deferred ART) and followed for a minimum of 3 years. The primary outcome is time to AIDS, SNA, or death. The study had a pilot phase to establish feasibility of accrual, which was set as the enrollment of at least 900 participants in the first year. Challenges encountered in the design and implementation of the study included the limited amount of data on the risk of a major component of the primary endpoint (SNA) in the study population, changes in treatment guidelines when the pilot phase was well underway, and the complexities of conducting the trial in a geographically wide population with diverse regulatory requirements. With the successful completion of the pilot phase, more than 1000 participants from 100 sites in 23 countries have been enrolled. The study will expand to include 237 sites in 36 countries to reach the target accrual of 4000 participants. START is addressing one of the most important questions in the clinical management of ART. The randomization provided a platform for the conduct of several substudies aimed at increasing our understanding of HIV disease and the effects of antiretroviral therapy beyond the primary question of the trial. The lessons learned from its design and implementation will hopefully be of use to future publicly funded international trials.
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影响因子：
1.9
作者：
DIGGLE, PJ
通讯作者：
DIGGLE, PJ
影响因子：
6.4
作者：
Boulware, David R.;Hullsiek, Katherine Huppler;Sereti, Irini
通讯作者：
Sereti, Irini
影响因子：
3.9
作者：
Benedict, RHB;Schretlen, D;Brandt, J
通讯作者：
Brandt, J
影响因子：
120.7
作者：
Burman, WJ;Reves, RR;Cohn, DL
通讯作者：
Cohn, DL
DOI：
10.1056/nejmoa0903175
发表时间：
2009-10-15
期刊：
The New England journal of medicine
影响因子：
--
作者：
INSIGHT-ESPRIT Study Group;SILCAAT Scientific Committee;Abrams D;Lévy Y;Losso MH;Babiker A;Collins G;Cooper DA;Darbyshire J;Emery S;Fox L;Gordin F;Lane HC;Lundgren JD;Mitsuyasu R;Neaton JD;Phillips A;Routy JP;Tambussi G;Wentworth D
通讯作者：
Wentworth D