Antiviral medications for preventing cytomegalovirus disease in solid organ transplant recipients

Background The risk of cytomegalovirus (CMV) infection in solid organ transplant recipients has resulted in the frequent use of prophylaxis with the aim of preventing the clinical syndrome associated with CMV infection. Objectives To determine the benefits and harms of antiviral medications to prevent CMV disease and all-cause mortality in solid organ transplant recipients. Search strategy We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, reference lists and abstracts from conference proceedings without language restriction. Date of last search : February 2007 Selection criteria Randomised controlled trials (RCTs) and quasi-RCTs comparing antiviral medications with placebo or no treatment, comparing different antiviral medications and comparing different regimens of the same antiviral medications in recipients of any solid organ transplant. Data collection and analysis Statistical analyses were performed using the random effects model and results expressed as relative risk (RR) for dichotomous outcomes with 95% confidence intervals (CI). Subgroup analysis and univariate meta-regression were performed using restricted maximuml-ikelihood to estimate the between study variance. Multivariate meta-regression was performed to investigate whether the results were altered after allowing for differences in drugs used, organ transplanted and recipient CMV serostatus at the time of transplantation. Main results Thirty four studies (3850 participants) were identified. Prophylaxis with aciclovir, ganciclovir or valaciclovir compared with placebo or no treatment significantly reduced the risk for CMV disease (19 studies; RR 0.42, 95% CI 0.34 to 0.52), CMV infection (17 studies; RR 0.61, 95% CI 0.48 to 0.77), and all-cause mortality (17 studies; RR 0.63, 95% CI 0.43 to 0.92) primarily due to reduced mortality from CMV disease (7 studies; RR 0.26, 95% CI 0.08 to 0.78). Prophylaxis reduced the risk of herpes simplex and herpes zoster disease, bacterial and protozoal infections but not fungal infection, acute rejection or graft loss. Meta-regression showed no significant difference in the relative benefit of treatment (risk of CMV disease or all-cause mortality) by organ transplanted or CMV serostatus; no conclusions were possible for CMV negative recipients of negative organs. In direct comparison studies, ganciclovir was more effective than aciclovir in preventing CMV disease (7 studies; RR 0.37, 95% CI 0.23 to 0.60). Valganciclovir and IV ganciclovir were as effective as oral ganciclovir. Authors' conclusions Prophylaxis with antiviral medications reduces CMV disease and CMV-associated mortality in solid organ transplant recipients. They should be used routinely in CMV positive recipients and in CMV negative recipients of CMV positive organ transplants. Keywords KeyWords Plus:HIGH-DOSE ACYCLOVIR; RANDOMIZED CONTROLLED-TRIAL; PREEMPTIVE GANCICLOVIR THERAPY; RENAL-ALLOGRAFT REJECTION; PLACEBO-CONTROLLED TRIAL; INTRAVENOUS IMMUNE GLOBULIN; LONG-TERM PROPHYLAXIS; VS. ORAL GANCICLOVIR; LIVER-TRANSPLANTATION; HEART-TRANSPLANTATION