Improved HIV-1 Viral Load Monitoring Capacity using Pooled Testing with Marker-Assisted Deconvolution

Abstract

Objective—Improve pooled viral load (VL) testing to increase HIV treatment monitoring capacity, particularly relevant for resource-limited settings. Design—We developed mMPA (marker-assisted mini-pooling with algorithm), a new VL pooling deconvolution strategy that utilizes 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. Methods—We simulated the use of pooled testing to ascertain virological failure status on 918 participants from three studies conducted at the Academic Model Providing Access to Healthcare (AMPATH) 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. Results—Using CD4 count as a marker to assist deconvolution, mMPA significantly reduces the number of VL assays by 52% (CI=48–57%), 40% (CI=38–42%), and 19% (CI=15–22%) compared with individual testing, simple mini-pooling, and mini-pooling with algorithm (MPA), respectively. mMPA has higher sensitivity and negative/positive predictive values than MPA, 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. Conclusions—mMPA can substantially increase the capacity of VL monitoring.