Antiviral medications to prevent cytomegalovirus disease and early death in recipients of solid-organ transplants: a systematic review of randomised controlled trials.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Hodson
Elisabeth M
EM
National Health and Medical Research Council Centre for Clinical Research Excellence, Centre for Kidney Research, The Children's Hospital at Westmead, Sydney, Australia. Elisah@chw.edu.au
Jones
Cheryl A
CA
Webster
Angela C
AC
Strippoli
Giovanni F M
GF
Barclay
Peter G
PG
Kable
Kathy
K
Vimalachandra
Dushyanthi
D
Craig
Jonathan C
JC
D000212:Acyclovir / Q000031:analogs & derivatives / Q000627:therapeutic use; D000998:Antiviral Agents / Q000627:therapeutic use*; D003586:Cytomegalovirus Infections / Q000517:prevention & control*; D015774:Ganciclovir / Q000627:therapeutic use; D006084:Graft Rejection; D006801:Humans; D009894:Opportunistic Infections / Q000517:prevention & control*; D016377:Organ Transplantation / Q000401:mortality; D016032:Randomized Controlled Trials as Topic; D000077483:Valacyclovir; D014633:Valine / Q000031:analogs & derivatives / Q000627:therapeutic use
D000998:Antiviral Agents; D014633:Valine; D000077483:Valacyclovir; D015774:Ganciclovir; D000212:Acyclovir