Liu Tao, Hogan Joseph W, Daniels Michael J, Coetzer Mia, Xu Yizhen, Bove Gerald, DeLong Allison K, Ledingham Lauren, Orido Millicent, Diero Lameck, Kantor Rami
*Department of Biostatistics and Center for Statistical Sciences, Brown University School of Public Health, Providence, RI; †Academic Model Providing Access to Healthcare (AMPATH), Eldoret, Kenya; Departments of ‡Statistics and Data Sciences; §Integrative Biology, University of Texas at Austin, Austin, TX; ‖Division of Infectious Diseases, the Alpert Medical School of Brown University, Providence, RI; and ¶Department of Medicine, School of Medicine, College of Health Sciences, Moi University, Eldoret, Kenya.
J Acquir Immune Defic Syndr. 2017 Aug 15;75(5):580-587. doi: 10.1097/QAI.0000000000001424.
Improve pooled viral load (VL) testing to increase HIV treatment monitoring capacity, particularly relevant for resource-limited settings.
We developed marker-assisted mini-pooling with algorithm (mMPA), a new VL pooling deconvolution strategy that uses information from low-cost, routinely collected clinical markers to determine an efficient order of sequential individual VL testing and dictates when the sequential testing can be stopped.
We simulated the use of pooled testing to ascertain virological failure status on 918 participants from 3 studies conducted at the Academic Model Providing Access to Healthcare in Eldoret, Kenya, and estimated the number of assays needed when using mMPA and other pooling methods. We also evaluated the impact of practical factors, such as specific markers used, prevalence of virological failure, pool size, VL measurement error, and assay detection cutoffs on mMPA, other pooling methods, and single testing.
Using CD4 count as a marker to assist deconvolution, mMPA significantly reduces the number of VL assays by 52% [confidence interval (CI): 48% to 57%], 40% (CI: 38% to 42%), and 19% (CI: 15% to 22%) compared with individual testing, simple mini-pooling, and mini-pooling with algorithm, respectively. mMPA has higher sensitivity and negative/positive predictive values than mini-pooling with algorithm, and comparable high specificity. Further improvement is achieved with additional clinical markers, such as age and time on therapy, with or without CD4 values. mMPA performance depends on prevalence of virological failure and pool size but is insensitive to VL measurement error and VL assay detection cutoffs.
mMPA can substantially increase the capacity of VL monitoring.
改进合并病毒载量（VL）检测，以提高HIV治疗监测能力，这对于资源有限的环境尤其重要。
我们开发了带有算法的标记辅助微池化法（mMPA），这是一种新的VL池解卷积策略，它利用低成本、常规收集的临床标记物信息来确定连续个体VL检测的有效顺序，并规定何时可以停止连续检测。
我们模拟使用合并检测来确定来自肯尼亚埃尔多雷特提供医疗服务的学术模型进行的3项研究中918名参与者的病毒学失败状态，并估计使用mMPA和其他合并方法时所需的检测次数。我们还评估了实际因素的影响, 如使用的特定标记物、病毒学失败的患病率、池大小、VL测量误差以及检测临界值对mMPA、其他合并方法和单样本检测的影响。
使用CD4计数作为辅助解卷积的标记物，与单样本检测、简单微池化法和带算法的微池化法相比，mMPA分别显著减少了52%[置信区间（CI）：48%至57%]、40%（CI：38%至42%）和19%（CI：15%至22%）的VL检测次数。mMPA比带算法的微池化法具有更高的灵敏度和阴性/阳性预测值，以及相当的高特异性。使用其他临床标记物（如年龄和治疗时间），无论有无CD4值，均可进一步改善。mMPA的性能取决于病毒学失败的患病率和池大小，但对VL测量误差和VL检测临界值不敏感。
mMPA可大幅提高VL监测能力。
