WITHDRAWN: Cytomegalovirus prophylaxis with antiviral agents for solid organ transplantation.

BACKGROUND: Cytomegalovirus (CMV) disease is a major cause of morbidity and mortality in solid organ transplantation. It is also associated with an increased risk of opportunistic infections, allograft injury and higher transplantation costs. CMV infection also seems to increase the risk of acute and chronic rejection of allografts via immune-mediated vascular injury. These serious consequences of CMV disease have lead to the development of effective strategies for the prevention, early diagnosis and treatment. However, there is no consensus on the necessity and the efficacy of CMV prophylaxis.

OBJECTIVES: To assess the efficacy of antiviral agents in solid organ transplant recipients in the prevention of cytomegalovirus infection and symptomatic disease and in the reduction of the incidence of acute rejection, graft loss and death.

SEARCH STRATEGY: A computerised search was conducted on Medline, Embase and Pascal. The reference lists of the current review articles and some congress proceedings were searched manually (Transplantation Proceedings, American Thoracic Society, European Society of Organ Transplantation).

SELECTION CRITERIA: Prospective, randomised studies in adults or paediatric recipients of a solid organ transplant, in which one arm received a prophylactic treatment with acyclovir and/or ganciclovir, started before cytomegalovirus infection, and the control arm received placebo or no treatment.

DATA COLLECTION AND ANALYSIS: Data were extracted from each trial and a letter sent to the authors to ask them to verify the data extracted, and to provide any data that was missing. For each outcome, several methods were used to calculate the chi-square for association and the estimate for the treatment effect with its 95% CI, with an additive model (rate difference), or a multiplicative model (odds ratio, relative risk). We considered the test of association to be significant when the p value was less than 0.01 and the homogeneity test to be significant when the p value was less than 0.1.

MAIN RESULTS: Prophylactic treatment was found to be associated with a significant decrease in cytomegalovirus disease compared with placebo or no treatment, using the logarithm of relative risk method (RR 0.51, 95% CI 0.41-0.64, p value for X(2) association < 0.001). Prophylactic treatment also decreased the rate of cytomegalovirus infection (RR 0.62, 95%CI 0.53-0.73, p < 0.001). Our analysis failed to show a significant decrease in graft loss, acute rejection or death in the prophylactic treatment group. Sub-group analysis based on the type of antiviral agent (acyclovir or ganciclovir) and on the type of organ (kidney or liver) gave comparable results.

AUTHORS' CONCLUSIONS: The use of antiviral agents for the prevention of cytomegalovirus disease and cytomegalovirus infection in solid organ transplantation is supported by this meta-analysis.