Viral-load kinetics and CMV disease

Abstract

Vincent Emery and colleagues (June 10, p 2032)1Emery VC Sabin CA Cope AV et al.Application of viral-load kinetics to identify patients who develop cytomegalovirus disease after transplantation.Lancet. 2000; 355: 2032-2036Summary Full Text Full Text PDF PubMed Scopus (442) Google Scholar predict early the risk of developing cytomegalovirus (CMV) disease after transplantation with a contour plot. Several caveats should however, be borne in mind when applying the results of this study to care of patients, and we propose recommendations to improve validity. First, the rate of increase in viral load might not represent the kinetics of viral replication. Emery and colleagues derived the rate from the viral load in the first CMV-PCR-positive sample (initial viral load) and the time between the last CMV-PCR-negative samples. Therefore, twopatients with the same initial viral load and sampling interval will have the same rate, even if they have totally different patterns of kinetics. Based on the plot, therefore, each patient is predicted to have the same-risk of developing CMV disease, which is not always true. An average of 57% of patients in Emery and colleagues' study had the initial viral load which was identical to the peak value. That is, their rates of increase in viral load after the day of the first CMV-PCR-positive result were zero or less, which are completely different from and cannot be represented by the calculated positive rates. To resolve this difficulty, one more viral load must be measured as quickly as possible after the first positive result. Thus, the rate of increase in viral load between the first and second positive samples should depict the kinetics and is available at an early stage. A new contour plot could be constructed if there is an association. Second, the contour plot is constructed by combining data from three different groups of patients (renal, liver, and bone-marrow recipients). Emery and colleagues show a significant difference in the peak CMV load among groups, as well as the initial viral load. These findings infer that each group had unique kinetics of viral replicaton. Consequently, this generalised plot is not appropriate to predict the risk, and a contour plot should have been done for each group. Finally, some values of the rate of change in CMV load in the contour plot exceed the range of the source data. For example, when a patient presenting with an initial viral load of 5 log10 genomes/mL blood and a rate of change of 0·1 log10 genomes/mL blood daily, the time between two consecutive samples is 27 days. This interval is longer than the maximum length of time (14 days) used in the study. Conversely, this rate is lower than the possible minimum rate (0.19 log10 genomes/mL blood per day). Without advising readers, however, this example was used in the text and a 33% risk was extrapolated. Therefore, to prevent the risk from extrapolating, a contour plot should have been presented within the range of data. Viral-load kinetics and CMV diseaseAuthors' reply Full-Text PDF