What are the benefits of giving regular antiviral medications to prevent cytomegalovirus disease, death and side effects in solid organ transplant recipients

Key messages

- In people who have received a solid organ transplant, giving antiviral medications reduces cytomegalovirus (CMV) disease and death from CMV disease, compared with placebo or no treatment.

- Longer periods of prophylaxis were found to be more effective than three months of therapy in kidney and lung transplant recipients.

- Low-dose valganciclovir was found to be as effective as the standard dose for preventing CMV in moderate-risk kidney transplant recipients.

Why use antiviral medication to prevent CMV disease in solid organ transplant recipients?

CMV (a herpes virus) is the most common type of virus in people who have received solid organ transplants(kidney, heart, liver, lung and pancreas). CMV is a major cause of illness and death during the first year after transplantation.

What did we want to find out?

We wanted to look at both the benefits and harms of antiviral medication to prevent CMV disease in people who have received a solid organ transplant.

What did we do?

We searched for all trials that assessed the benefits and harms of randomly allocated antiviral treatment for the prevention of CMV disease in people receiving a solid organ transplant. We compared and summarised the results of the trials and rated our confidence in the information based on factors such as trial methods and sizes.

What did we find?

We included 41 studies involving 5051 people who received a kidney, kidney and pancreas, liver, heart, lung, or heart and lung transplant. We found some antiviral drugs (ganciclovir, valaciclovir and aciclovir) reduced the risk of CMV disease, death due to CMV disease, and clinical disease caused by herpes simplex compared with placebo or no treatment. For CMV disease and death, the benefits of aciclovir, ganciclovir, and valaciclovir were seen across people who received heart, kidney or liver transplants. These benefits occur in both those recipients who had had CMV infection in the past, as well as in those recipients who have not had CMV before but who received a transplant from a donor who had had CMV infection in the past. The benefits occurred at all time points. We found that ganciclovir is more effective than aciclovir and as effective as valganciclovir, which is currently the most commonly used antiviral drug to prevent CMV disease in transplant recipients. Different doses of valganciclovir did not result in a difference in preventing CMV disease.

What are the limitations of the evidence?

Future studies may be required in the seronegative donor-recipient group depending on the prevalence of CMV disease in this group with newer and more potent immunosuppressive regimens.

More information is required on the efficacy of prophylaxis with different regimens of immunosuppressive regimens used for the prevention and treatment of rejection in different organ transplants.

How up-to-date is the evidence?

The evidence is up-to-date as of February 2024.

Authors' conclusions: 

Prophylaxis with antiviral medications reduces CMV disease and CMV-associated death, compared with placebo or no treatment, in solid organ transplant recipients. These data support the continued routine use of antiviral prophylaxis in CMV-positive recipients and CMV-negative recipients of CMV-positive organ transplants.

Read the full abstract...

The risk of cytomegalovirus (CMV) infection in solid organ transplant recipients has resulted in the frequent use of prophylaxis to prevent the clinical syndrome associated with CMV infection. This is an update of a review first published in 2005 and updated in 2008 and 2013.


To determine the benefits and harms of antiviral medications to prevent CMV disease and all-cause death in solid organ transplant recipients.

Search strategy: 

We contacted the information specialist and searched the Cochrane Kidney and Transplant Register of Studies up to 5 February 2024 using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov.

Selection criteria: 

We included randomised controlled trials (RCTs) and quasi-RCTs comparing antiviral medications with placebo or no treatment, comparing different antiviral medications or different regimens of the same antiviral medications for CMV prophylaxis in recipients of any solid organ transplant. Studies examining pre-emptive therapy for CMV infection are studied in a separate review and were excluded from this review.

Data collection and analysis: 

Two authors independently assessed study eligibility, risk of bias and extracted data. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes and mean difference (MD) and 95% CI for continuous outcomes. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.

Main results: 

This 2024 update found four new studies, bringing the total number of included studies to 41 (5054 participants). The risk of bias was high or unclear across most studies, with a low risk of bias for sequence generation (12), allocation concealment (12), blinding (11) and selective outcome reporting (9) in fewer studies.

There is high-certainty evidence that prophylaxis with aciclovir, ganciclovir or valaciclovir compared with placebo or no treatment is more effective in preventing CMV disease (19 studies: RR 0.42, 95% CI 0.34 to 0.52), all-cause death (17 studies: RR 0.63, 95% CI 0.43 to 0.92), and CMV infection (17 studies: RR 0.61, 95% CI 0.48 to 0.77). There is moderate-certainty evidence that prophylaxis probably reduces death from CMV disease (7 studies: RR 0.26, 95% CI 0.08 to 0.78). Prophylaxis reduces the risk of herpes simplex and herpes zoster disease, bacterial and protozoal infections but probably makes little to no difference to fungal infection, acute rejection or graft loss. No apparent differences in adverse events with aciclovir, ganciclovir or valaciclovir compared with placebo or no treatment were found.

There is high certainty evidence that ganciclovir, when compared with aciclovir, is more effective in preventing CMV disease (7 studies: RR 0.37, 95% CI 0.23 to 0.60). There may be little to no difference in any outcome between valganciclovir and IV ganciclovir compared with oral ganciclovir (low certainty evidence). The efficacy and adverse effects of valganciclovir or ganciclovir were probably no different to valaciclovir in three studies (moderate certainty evidence). There is moderate certainty evidence that extended duration prophylaxis probably reduces the risk of CMV disease compared with three months of therapy (2 studies: RR 0.20, 95% CI 0.12 to 0.35), with probably little to no difference in rates of adverse events. Low certainty evidence suggests that 450 mg/day valganciclovir compared with 900 mg/day valganciclovir results in little to no difference in all-cause death, CMV infection, acute rejection, and graft loss (no information on adverse events). Maribavir may increase CMV infection compared with ganciclovir (1 study: RR 1.34, 95% CI: 1.10 to 1.65; moderate certainty evidence); however, little to no difference between the two treatments were found for CMV disease, all-cause death, acute rejection, and adverse events at six months (low certainty evidence).