Prediction of cytomegalovirus (CMV) plasma load from evaluation of CMV whole-blood load in samples from renal transplant recipients

Abstract

In a prospective cohort of 82 renal transplant recipients, we evaluated the capacity of the cytomegalovirus (CMV) load in whole blood (WB) to predict the plasma CMV load, aiming to identify active CMV infections by using WB samples only and to deduce a WB threshold. Using quantitative real-time PCR, a total of 1,474 WB samples were assayed, of which 279 were positive for CMV, and 140 out of the 276 paired plasma samples tested positive. Thirty (36.6%) patients presented with at least one positive plasma PCR result, and 21 infection episodes (19 patients) required curative treatment (median follow-up time, 12 months). When the plasma CMV load was >500 copies/ml (n = 70), more than 94% (95% confidence interval, 86.0%, 98.4%) of WB samples had >500 copies/ml. Two prediction models were built: log(10) plasma viral load (VL) was calculated as -0.3777 + 0.9342 x log(10) WB VL and as -0.3777 + 0.8563 x log(10) WB VL for patients with and without treatment, respectively. In the validation sample (578 routine samples), 77.2% of the observed and expected plasma viral loads were concordant (95% confidence intervals, 73.5 and 80.5%). According to the model, the plasma viral load was >500 copies/ml when the WB load was >3,170 or >4,000 copies/ml in patients with or without treatment, respectively. WB seems to be an appropriate candidate for routine CMV monitoring of transplant recipients by using a single assay.

FIG. 1.

Follow-up of the 82 patients, with distribution of real-time quantitative PCR results for WB and plasma (PL). cop, copies.

FIG. 2.

Prediction of plasma (PL) VL from WB VL (n = 147). cp or cop, copies. Of note, some of the viral DNA loads in plasma were undetectable (i.e., left-censored) and are plotted at the detection limit (2.70 log₁₀ copies/ml); however, they were taken into account as left-censored values in the model (see Materials and Methods).

FIG. 3.

Distribution of WB and plasma (PL) real-time quantitative PCR results for the 82 patients without treatment. cop, copies.