即刻与延迟启动抗逆转录病毒治疗的符合方案效应。
The per-protocol effect of immediate versus deferred antiretroviral therapy initiation.
作者信息
Lodi Sara, Sharma Shweta, Lundgren Jens D, Phillips Andrew N, Cole Stephen R, Logan Roger, Agan Brian K, Babiker Abdel, Klinker Hartwig, Chu Haitao, Law Matthew, Neaton James D, Hernán Miguel A
机构信息
aDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts bDivision of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA cDepartment of Infectious Diseases, Rigshospitalet, University of Copenhagen, København, Denmark dResearch Department of Infection & Population Health, University College London, London, United Kingdom eDepartment of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina fInfectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences gHenry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, USA hMedical Research Council, Clinical Trials Unit in University College London, London, United Kingdom iUniversity of Wuerzburg Medical Center, Würzburg, Germany jThe Kirby Institute, Sydney, Australia kDepartment of Biostatistics, Harvard T.H. Chan School of Public Health lHarvard-MIT Division of Health Sciences and Technology, Boston, Massachusetts, USA.
出版信息
AIDS. 2016 Nov 13;30(17):2659-2663. doi: 10.1097/QAD.0000000000001243.
OBJECTIVE
The Strategic Timing of AntiRetroviral Treatment (START) trial found a lower risk of a composite clinical outcome in HIV-positive individuals assigned to immediate initiation of antiretroviral therapy (ART) compared with those assigned to deferred initiation. However, 30% of those assigned to deferred initiation started ART earlier than the protocol specified. To supplement the published intention-to-treat (ITT) effect estimates, here we estimate the per-protocol effect of immediate versus deferred ART initiation in START.
DESIGN
The START trial randomized 4685 HIV-positive participants with CD4 cell counts more than 500 cells/μl to start ART immediately after randomization (immediate initiation group) or to wait until the CD4 cell count dropped below 350 cells/μl or an AIDS diagnosis (deferred initiation group).
METHODS
We used the parametric g-formula to estimate and compare the cumulative 5-year risk of the composite clinical outcome in the immediate initiation group, and deferred initiation groups had all the trial participants adhered to the protocol.
RESULTS
We estimated that the 5-year risk of the composite outcome would have been 3.2% under immediate ART initiation and 7.0% under deferred initiation. The difference of 3.8% (95% confidence interval 1.5, 6.5) was larger than the ITT effect estimate of 3.1%, corresponding to a difference in effect estimates of 0.72% (-0.35, 2.35).
CONCLUSION
The ITT effect estimate may underestimate the benefit of immediate ART initiation by 23%. This estimate can be used by patients and policy-makers who need to understand the full extent of the benefit of changes in ART initiation policies.
目的
抗逆转录病毒治疗时机战略（START）试验发现，与延迟启动抗逆转录病毒治疗（ART）的HIV阳性个体相比，立即启动ART的个体发生综合临床结局的风险更低。然而，30%被分配到延迟启动组的个体开始ART的时间比方案规定的更早。为补充已发表的意向性分析（ITT）效应估计值，我们在此估计START试验中立即启动与延迟启动ART的符合方案效应。
设计
START试验将4685名CD4细胞计数超过500个/μl的HIV阳性参与者随机分为两组，一组在随机分组后立即开始ART（立即启动组），另一组等到CD4细胞计数降至350个/μl以下或确诊为艾滋病时开始（延迟启动组）。
方法
我们使用参数化g公式来估计和比较立即启动组和延迟启动组（所有试验参与者均遵守方案）中综合临床结局的累积5年风险。
结果
我们估计，立即启动ART时综合结局的5年风险为3.2%，延迟启动时为7.0%。3.8%（95%置信区间1.5，6.5）的差异大于ITT效应估计值3.1%，相应的效应估计值差异为0.72%（-0.35，2.35）。
结论
ITT效应估计值可能低估了立即启动ART的益处23%。这一估计值可供需要了解ART启动政策变化全部益处的患者和政策制定者使用。
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