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. 2012 Sep;12(9):2457-64.
doi: 10.1111/j.1600-6143.2012.04087.x. Epub 2012 May 17.

Cytomegalovirus replication kinetics in solid organ transplant recipients managed by preemptive therapy

S F Atabani  1 , C Smith, C Atkinson, R W Aldridge, M Rodriguez-Perálvarez, N Rolando, M Harber, G Jones, A O'Riordan, A K Burroughs, D Thorburn, J O'Beirne, R S B Milne, V C Emery, P D Griffiths
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Free PMC article

Cytomegalovirus replication kinetics in solid organ transplant recipients managed by preemptive therapy

S F Atabani et al. Am J Transplant. 2012 Sep.
Free PMC article

Abstract

After allotransplantation, cytomegalovirus (CMV) may be transmitted from the donor organ, giving rise to primary infection in a CMV negative recipient or reinfection in one who is CMV positive. In addition, latent CMV may reactivate in a CMV positive recipient. In this study, serial blood samples from 689 kidney or liver transplant recipients were tested for CMV DNA by quantitative PCR. CMV was managed using preemptive antiviral therapy and no patient received antiviral prophylaxis. Dynamic and quantitative measures of viremia and treatment were assessed. Median peak viral load, duration of viremia and duration of treatment were highest during primary infection, followed by reinfection then reactivation. In patients who experienced a second episode of viremia, the viral replication rate was significantly slower than in the first episode. Our data provide a clear demonstration of the immune control of CMV in immunosuppressed patients and emphasize the effectiveness of the preemptive approach for prevention of CMV syndrome and end organ disease. Overall, our findings provide quantitative biomarkers which can be used in pharmacodynamic assessments of the ability of novel CMV vaccines or antiviral drugs to reduce or even interrupt such transmission.

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Figures

Figure 1
Figure 1. Kaplan–Meier survival analysis for CMV viremia, indicating the proportion of patients in each of the four DR groups remaining viremia-free through the 90 day follow-up period
p < 0.0001 (log-rank test) for a comparison between the groups.
Figure 2
Figure 2. Pie charts illustrating the proportion of individuals in each DR group among
(A) The total patient cohort; (B) those with viremia posttransplant, (C) those who received antiviral therapy; (D) those with CMV syndrome.
Figure 3
Figure 3. Frequency distribution plots of the values of peak viral load among the three DR groups of patients at risk of CMV infection
Bin size is 0.2 Log 10 genomes. p-Values indicate difference from Gaussian distribution and were calculated with the D’Agostino & Pearson omnibus K2 normality test.
Figure 4
Figure 4. Peak viral loads in the three DR groups of liver (A) and renal (B) transplant patients at risk of CMV infections
Line shows median value, box shows interquartile range and bars indicate range. p-Values are given only for significant differences.
Figure 5
Figure 5. Duration of viremia (A, B) and duration of therapy (C, D) in the three DR groups of liver (A & C) and renal (B & D) transplant patients at risk of CMV infections
Line shows median value, box shows interquartile range, and bars indicate range. p-Values are given only for significant differences.
See this image and copyright information in PMC

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