Human cytomegalovirus (HCMV) replication kinetics in stem cell transplant recipients following anti-HCMV therapy

Abstract

Background Cytomegalovirus (HCMV) remains an important infection following stem cell transplantation (SCT) and is managed via pre-emptive therapy. In some patients HCMV loads continue to increase after therapy and they experience multiple episodes of replication. Objectives To identify the risk factors associated with failure to immediately control HCMV replication after antiviral therapy and for recurrence of replication. Study design Replication kinetics of human cytomegalovirus (HCMV) were studied a cohort of 153 T-cell depleted allogeneic SCT patients. Results In 57 patients (31%) who experienced HCMV DNAemia, the mean growth rate of HCMV was 0.35 day −1 equivalent to a doubling time of 2.2 days. In patients requiring anti-HCMV treatment with either ganciclovir or ganciclovir/foscarnet ( n = 49), HCMV load increased to a peak value of >2 days after initiation of therapy in 21 patients and only the growth rate prior to therapy was a risk factor (Odds ratio = 1.4 per 0.1 day −1 increase; p = 0.004). In patients where antiviral intervention occurred after peak virus load the decline rate of HCMV load was accelerated 4-fold if the patient was subsequently initiated on anti-HCMV therapy ( p = 0.02). A subset of patients (38%) experienced a recurrence of their DNAemia at a mean of 20 days after the cessation of their first replication episode and this was only associated with receiving stem cells from a seronegative donor (Odds ratio = 6.59; p < 0.001). Conclusions The kinetics of response to therapy is closely associated with HCMV replication kinetics prior to therapy while recurrence of replication is associated with HCMV serostatus of the donor.