Modeling the causal effect of treatment initiation time on survival: Application to HIV/TB co-infection.

Modeling the causal effect of treatment initiation time on survival: Application to HIV/TB co-infection.
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DOI:
10.1111/biom.12780
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发表时间:
2018-06
期刊:
影响因子:
1.9
通讯作者:
Siika A
Siika A
中科院分区:
数学3区
文献类型:
--
作者:
Hu L;Hogan JW;Mwangi AW;Siika A

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艾滋病毒和结核病(TB)合并感染患者开始抗逆转录病毒治疗(ART)的时机需要仔细考虑。CD 4细胞计数可用于指导何时开始ART的决策。最近的随机试验和观察性研究的证据通常支持早期启动,但没有提供关于启动时间对连续规模的影响的信息。在本文中,我们开发并应用了一个高度灵活的结构比例风险模型,用于表征治疗开始时间对生存分布的影响。该模型可以使用加权偏似然评分函数来拟合。评分函数和权重的构建必须适应治疗开始时间、结局或两者的删失。该方法适用于4903个人的艾滋病毒/结核病合并感染的数据,来自电子健康记录在肯尼亚的一个大型艾滋病毒护理计划。我们使用的模型配方,灵活地捕捉ART启动时间和ART持续时间使用自然三次样条的联合效果。该模型用于生成对应于特定治疗开始时间的生存曲线;并确定TB诊断时由CD 4计数定义的亚组的ART开始的最佳时间。我们的研究结果可能提供关于ART时机和死亡率之间关系的“更高分辨率”信息,以及关于ART时机在CD 4亚组中的差异效应。
The timing of antiretroviral therapy (ART) initiation for HIV and tuberculosis (TB) co-infected patients needs to be considered carefully. CD4 cell count can be used to guide decision making about when to initiate ART. Evidence from recent randomized trials and observational studies generally supports early initiation but does not provide information about effects of initiation time on a continuous scale. In this paper, we develop and apply a highly flexible structural proportional hazards model for characterizing the effect of treatment initiation time on a survival distribution. The model can be fitted using a weighted partial likelihood score function. Construction of both the score function and the weights must accommodate censoring of the treatment initiation time, the outcome, or both. The methods are applied to data on 4903 individuals with HIV/TB co-infection, derived from electronic health records in a large HIV care program in Kenya. We use a model formulation that flexibly captures the joint effects of ART initiation time and ART duration using natural cubic splines. The model is used to generate survival curves corresponding to specific treatment initiation times; and to identify optimal times for ART initiation for subgroups defined by CD4 count at time of TB diagnosis. Our findings potentially provide ‘higher resolution’ information about the relationship between ART timing and mortality, and about the differential effect of ART timing within CD4 subgroups.
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