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Antiviral medications for preventing cytomegalovirus disease in solid organ transplant recipients

  • Review
  • Intervention

Authors

  • Elisabeth M Hodson,

    Corresponding author
    1. b) School of Public Health, The University of Sydney, a) Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, NSW, Australia
    • Elisabeth M Hodson, a) Centre for Kidney Research, The Children's Hospital at Westmead, b) School of Public Health, The University of Sydney, Locked Bag 4001, Westmead, NSW, 2145, Australia. Elisah@chw.edu.au.

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  • Jonathan C Craig,

    1. (b) School of Public Health, The University of Sydney, (a) Cochrane Renal Group, Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, NSW, Australia
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  • Giovanni FM Strippoli,

    1. c) Diaverum Medical Scientific office, d) Mario Negri Sud Consortium, Italy, a) School of Public Health, University of Sydney, b) Cochrane Renal Group, Westmead, NSW, Australia
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  • Angela C Webster

    1. (c) School of Public Health, University of Sydney, (a) Cochrane Renal Group, Centre for Kidney Research, The Children's Hospital at Westmead, (b) Centre for Transplant and Renal Research, Westmead Millennium Institute, University of Sydney at Westmead Hospital, Sydney, NSW, Australia
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Abstract

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 methods

We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, reference lists and abstracts from conference proceedings without language restriction.

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 risk ratio (RR) for dichotomous outcomes with 95% confidence intervals (CI). Subgroup analysis and univariate meta-regression were performed using restricted maximum-likelihood 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.

Plain language summary

Prophylaxis with antiviral medications reduces CMV disease and CMV-associated mortality in solid organ transplant recipients

Cytomegalovirus (CMV) is the most common virus pathogen in solid organ transplant recipients (kidney, heart, liver, lung and pancreas) being a major cause of morbidity and mortality during the first six months after transplantation. Two main strategies to prevent CMV disease have been adopted: prophylaxis of organ recipients with antiviral agents, or 'pre-emptive therapy' of organ recipients, who develop evidence of CMV infection during routine screening. This review looked at the benefits and harms of antiviral medication to prevent CMV disease in solid organ transplant recipients. Thirty four studies (3840 participants) were identified. This review shows that the antiviral medications, ganciclovir, valaciclovir and aciclovir reduced the risk of CMV disease, all-cause mortality due to reduced mortality from CMV disease, clinical disease caused by herpes simplex and herpes zoster, bacterial infections and protozoal infections. For CMV disease and mortality, the relative benefits of aciclovir, ganciclovir and valaciclovir appear consistent across recipients of heart, kidney and liver transplants. These benefits occur in both CMV positive recipients and CMV negative recipients of CMV positive organs, are irrespective of whether immunosuppression includes antilymphocyte antibody therapy and are not dependent on the time of outcome assessment. In comparison studies, ganciclovir is more effective than aciclovir and as effective as valganciclovir, which is currently the most commonly used antiviral medication to prevent CMV disease in transplant recipients. More studies are needed in lung and heart transplant recipients and to determine the optimum duration and dosage of medications for all solid organ transplant recipients.

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