标题： 治愈性HIV治疗的因果间接效应：受检测限和测量误差影响的中介变量 显示英文标题

标题： Causal indirect effect of an HIV curative treatment: mediators subject to an assay limit and measurement error

摘要： 因果中介分析将处理对结果的总效应分解为通过中介变量的间接效应和其他路径的直接效应。 只能估计相对于无处理的纯间接效应/间接效应，而不是通过假设处理对中介变量的影响与无处理的结果数据结合而得到的总效应。 此外，无论结果模型中处理和中介变量之间是否存在交互作用，中介公式都适用于纯间接效应（或相对于无处理的有机间接效应）。 这种方法在基于其间接效应选择有前景的治疗方案以进一步在随机临床试验中评估方面具有重要意义。 我们将这种方法应用于评估两种HIV持续性测量中哪一种是未来HIV治愈治疗更有前景的目标。 我们结合对两个中介变量的假设处理效应以及无处理的结果数据，以比较针对这些中介变量的治疗的间接效应。 一些HIV持续性测量值低于检测限，导致左删失的中介变量。 我们通过假设结果模型适用于低于检测限的中介变量并使用最大似然估计来解决这个问题。 为了处理中介变量中的测量误差，我们调整了我们的估计。 使用已完成的ACTG研究数据，我们估计潜在的治愈性HIV治疗通过HIV持续性测量在HIV药物中断后第4周和第8周的病毒抑制中的纯间接效应或有机间接效应。 显示英文摘要

摘要： Causal mediation analysis decomposes the total effect of a treatment on an outcome into the indirect effect, operating through the mediator, and the direct effect, operating through other pathways. One can estimate only the pure indirect effect/indirect effect relative to no treatment, rather than the total effect by combining a hypothesized treatment effect on the mediator with outcome data without treatment. Furthermore, the mediation formula holds for the pure indirect effect (or the organic indirect effect relative to no treatment) regardless of whether there is an interaction between the treatment and mediator in the outcome model. This methodology holds significant promise in selecting prospective treatments based on their indirect effect for further evaluation in randomized clinical trials. We apply this methodology to assess which of two measures of HIV persistence is a more promising target for future HIV curative treatments. We combine a hypothesized treatment effect on two mediators, and outcome data without treatment, to compare the indirect effect of treatments targeting these mediators. Some HIV persistence measurements fall below the assay limit, leading to left-censored mediators. We address this by assuming the outcome model extends to mediators below the assay limit and use maximum likelihood estimation. To address measurement error in the mediators, we adjust our estimates. Using data from completed ACTG studies, we estimate the pure or organic indirect effect of potential curative HIV treatments on viral suppression through weeks 4 and 8 after HIV medication interruption, mediated by HIV persistence measures.