Clinically Applied Variation in Replication Kinetics During Episodes of Post-Transplant Cytomegalovirus (CMV) Infections
Background: CMV infection in transplant recipients is known to evolve rapidly, with a doubling time (DT) of 1.2-2 days, necessitating weekly intervals between screening with CMV PCR to diagnose emerging infections while viral load remains low. We investigated the reproducibility of the DT estimate in our large cohort of unselected transplant recipients.
Methods: Recipients of hematopoietic stem cell (n=119) or solid organ transplant (n=74) with a first CMV infection within the first year after transplantation were included. CMV DT was calculated using viral loads over first week of infection as previously published (Emery et al, JEM 1999). We also estimated, using mathematical simulation of a theoretical cohort, the % with an undesirably high CMV viral load (see table) depending on CMV PCR screening intervals and variation in DT.
Results: Among 193 first CMV infection episodes, the overall observed median DT was 4.3 days (IQR 2.5-7.8). This estimate persisted after stratifying for CMV-infection susceptibility (i.e. prior CMV immunity), and types of transplantation (p>0.4). In a simulated cohort, the % of emerging infections between two screening intervals diagnosed with an undesirably high viral load depended on the screening interval and the DT (table). Assuming a fixed DT of 31 or 36 hours, an unacceptably high rate of diagnoses at undesirably high viral load (16.7-33.3%) was observed if the screening interval was extended from 7 to 10 days (i.e. 30% fewer screening visits). Conversely, this % remained low (4.3%) when applying the varied DT observed in our cohort.
Conclusion: The DT for post-transplant CMV infections in our cohort was twice as long as previously reported and with remarkable variation. No discernable risk factors associated with the variation in DT within our cohort and when compared to previously reported figures from other sites could be identified, although important possible contributors such as viral fitness or T-cell immunological competence were unavailable. Our findings suggest that in similar settings to ours, it is safe to extend the intervals between screening with CMV PCR from 7 to 10 days (i.e. a 30% reduction in screening visits and associated cost); a suggestion that should be prospectively validated.
C. Møller Frederiksen, None
F. Gustafsson, None
M. Iversen, None
N. Kirkby, None
A. Rasmussen, None
S. Schwartz Sørensen, None
H. Sengeløv, None
L. Vindeløv, None
J. Grarup, None
J. Lundgren, None