Application of viral-load kinetics to identify patients who develop cytomegalovirus disease after transplantation

Background Cytomegalovirus (CMV) continues to be a major problem post-transplantation; early markers for predicting patients at risk of CMV disease are needed. Peak CMV load in the blood correlates with CMV disease but frequently occurs too late to provide prognostic information. Methods 359 transplant recipients (162 liver, 87 renal, and 110 bone marrow) were prospectively monitored for CMV DNA in the blood with qualitative and quantitative PCR. 3873 samples were analysed. The CMV load in the first PCR-positive sample and the rate of increase in CMV load in blood during the initial phase of replication were assessed as risk factors for CMV disease using logistic regression. Findings 127 of the 359 patients had CMV DNA in the blood and 49 developed CMV disease. initial viral load correlated significantly with peak CMV load (R-2=0.47, p=<0.001) and with CMV disease (odds ratio 1.82 [95% CI 1.11-2.98; p=0.02; 1.34 [1.07-1.68] p=0.01, and 1.52 [1.13-2.05], p=0.006, per 0.25 log(10) increase in viral load for liver, renal, and bone-marrow patients, respectively). The rate of increase in CMV load between the last PCR-negative and first PCR-positive sample was significantly faster in patients with CMV disease (0.33 log(10) versus 0.19 log(10) genomes/mL daily, p<0.001). In multivariate-regression analyses, both initial CMV load and rate of viral load increase were independent risk factors for CMV disease (1.28 [1.06-1.52], p=0.01, per 0.25 log(10) increase in CMV load and 1.52 [1.06-2.17], p=0.02, per 0.1 log(10) increase in CMV load/mL daily, respectively). Interpretation CMV load in the initial phase of active infection and the rate of increase in viral load both correlate with CMV disease in transplant recipients; in combination, they have the potential to identify patients at imminent risk of CMV disease.