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

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.