An International Multicenter Performance Analysis of CMV Viral Load Tests.

Background. Quantification of CMV viral load is central to the management of CMV infections in immunocompromised patients, but quantitative results currently differ significantly across methods and laboratories.Methods. The COBAS(®) AmpliPrep/COBAS(®) TaqMan(®) CMV Test [CAP/CTM CMV test]), developed using the 1st World Health Organization CMV standard in the calibration process, was compared to local assays used by five laboratories at transplant centers in the United States and Europe. Blinded plasma panels (N=90) spiked with 2.18-6.7 log(10) copies/mL and clinical plasma samples from immunocompromised patients (N=660) were tested.Results. Observed mean panel member concentrations by site and 95% confidence intervals (CI) of the data combined across sites were narrower for CAP/CTM CMV test compared to local assays. 95% CI in log(10)-copies/mL of the combined data per panel member for CAP/CTM CMV test vs. comparator assays was 0.17 vs. 1.5 at 2.18 log(10)-copies/mL; 0.14 vs. 0.52 at 2.74 log(10)-copies/mL; 0.16 vs. 0.6 at 3.3 log(10)-copies/mL; 0.2 vs. 1.11 at 4.3 log(10)-copies/mL; 0.21 vs. 1.13 at 4.7 log(10)-copies/mL; 0.18 vs. 1.4 at 6.7 log(10)-copies/mL. In clinical specimens, constant and variable quantification differences between CAP/CTM CMV test and comparator assays were observed.Conclusions. High inter-laboratory agreement and precision of CAP/CTM CMV test results across five different laboratories over four orders of magnitude suggest that this assay could be valuable in prospective studies identifying clinical viral load thresholds for CMV treatment.