Hodson, E. M. et al. Antiviral medications to prevent cytomegalovirus disease and early death in recipients of solid-organ transplants: a systematic review of randomised controlled trials. Lancet 365, 2105-2115

National Health and Medical Research Council Centre for Clinical Research Excellence, Centre for Kidney Research, The Children's Hospital at Westmead, Sydney, Australia.
The Lancet (Impact Factor: 45.22). 06/2005; 365(9477):2105-15. DOI: 10.1016/S0140-6736(05)66553-1
Source: PubMed


Antiviral prophylaxis is commonly used in recipients of solid-organ transplants with the aim of preventing the clinical syndrome associated with cytomegalovirus infection. We undertook a systematic review to investigate whether this approach affects risks of cytomegalovirus disease and death.
Randomised controlled trials of prophylaxis with antiviral medications for cytomegalovirus disease in solid-organ-transplant recipients were identified. Data were combined in meta-analyses by a random-effects model.
Compared with placebo or no treatment, prophylaxis with aciclovir, ganciclovir, or valaciclovir significantly reduced the risks of cytomegalovirus disease (19 trials, 1981 patients; relative risk 0.42 [95% CI 0.34-0.52]), cytomegalovirus infection (17 trials, 1786 patients; 0.61 [0.48-0.77]), and all-cause mortality (17 trials, 1838 patients; 0.63 [0.43-0.92]), mainly owing to lower mortality from cytomegalovirus disease (seven trials, 1300 patients; 0.26 [0.08-0.78]). Prophylaxis also lowered the risks of disease caused by herpes simplex or zoster virus, bacterial infections, and protozoal infections, but not fungal infection, acute rejection, or graft loss. Meta-regression showed no significant difference in the risk of cytomegalovirus disease or all-cause mortality by organ transplanted or cytomegalovirus serostatus; no conclusions were possible for cytomegalovirus-negative recipients of negative organs. In trials of direct comparisons, ganciclovir was more effective than aciclovir in preventing cytomegalovirus disease. Valganciclovir and intravenous ganciclovir were as effective as oral ganciclovir.
Prophylaxis with antiviral medications reduces the risk of cytomegalovirus disease and associated mortality in recipients of solid-organ transplants. This approach should be used routinely in cytomegalovirus-positive recipients and in cytomegalovirus-negative recipients of organs positive for the virus.

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    • "retinitis, neurological, gastrointestinal and pulmonary disease) in immunosuppressed individuals. Second, in solid organ transplantation, an epidemiological association between CMV infection and acute rejection has been established [2] [4] [5]. The CMV serostatus of donors (D) and recipients (R) has a direct impact on the occurrence of acute rejection: D + /R − combinations present the highest risk of acute rejection [6]. "
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    • "Same conclusions were obtained in studies that used the ganciclovir as antiviral therapy [48]. A metaanalysis of 32 trials (3737 patients) performed to compare outcomes for various prophylactic antivirals for transplant patients at risk for CMV disease demonstrated that prophylaxis decreased CMV disease, CMV infection, and all-cause mortality [49]. This meta-analysis showed that ganciclovir was more effective than acyclovir in preventing CMV disease. "
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    • "Importantly, treatment of heart transplant recipients with ganciclovir, a potent inhibitor of viral replication and HCMV disease, delayed the time to the development of allograft rejection, demonstrating that viral replication is important for acceleration of disease (Merigan et al., 1992; Valantine et al., 1999). Furthermore, kidney transplant allograft survival was decreased in asymptomatic HCMV-infected recipients during the first 100 days post transplantation compared to patients with no HCMV infection suggesting that the presence of HCMV alone, whether asymptomatic or with overt infection, has a negative impact on graft survival (Hodson et al., 2005). Similarly, using rat heart, kidney, lung and small bowel transplantation models of chronic rejection, it has been shown that acute infection with ratCMV (RCMV) dramatically decreases the mean time to graft failure, and also increases the degree of vasculopathy in the allograft vessels (Orloff et al., 2002; Orloff et al., 2000; Streblow et al., 2003). "
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