Pre-emptive treatment with antiviral agents can help to reduce the risk of cytomegalovirus disease

Cytomegalovirus (CMV) is the most common cause of viral disease in people who have received kidney, heart, liver, lung or pancreas transplants (solid organ transplants). CMV is a major cause of illness and death during the first six months after transplantation. Characteristics of CMV include fever, very low white blood cell counts (leucopenia) and very low numbers of platelets (thrombocytopenia) with or without specific organ involvement.

Two main strategies to prevent CMV disease have been adopted: giving daily low doses of an antiviral agent (prophylaxis) to all organ transplant recipients, or prescribing an antiviral agent when an organ transplant recipient develops laboratory-confirmed evidence of infection during routine screening (pre-emptive treatment).

This review looked at the benefits and harms of pre-emptive treatment with antiviral agents in preventing CMV disease in solid organ transplant recipients. We identified six studies (288 participants) that compared pre-emptive treatment with placebo or usual care. Pre-emptive treatment significantly reduced the risk of CMV disease. There were also eight studies (784 participants) that compared pre-emptive treatment with antiviral prophylaxis. There were no significant differences in the risks of CMV disease or death between pre-emptive therapy and prophylaxis. However, variation in results among studies meant that there is some uncertainty about these results.

Low white blood cell counts were much less common with pre-emptive treatment.

More studies comparing pre-emptive treatment with antiviral prophylaxis are still required to provide greater certainty about the relative effectiveness of pre-emptive therapy compared with prophylaxis.

Authors' conclusions: 

Few RCTs have evaluated the effects of pre-emptive therapy to prevent CMV disease. Pre-emptive therapy is effective compared with placebo or standard care. Despite the inclusion of five additional studies in this update, the efficacy of pre-emptive therapy compared with prophylaxis to prevent CMV disease remains unclear due to significant heterogeneity between studies. Additional head-to-head studies are required to determine the relative benefits and harms of pre-emptive therapy and prophylaxis to prevent CMV disease in solid organ transplant recipients.

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Background: 

Cytomegalovirus (CMV) is a significant cause of morbidity and mortality in solid organ transplant recipients. Pre-emptive treatment of patients with CMV viraemia using antiviral agents has been suggested as an alternative to routine prophylaxis to prevent CMV disease. This is an update of a Cochrane review first published in 2005.

Objectives: 

This review was conducted to evaluate the efficacy of pre-emptive treatment with antiviral medications in preventing symptomatic CMV disease.

Search strategy: 

For this update, we searched the Cochrane Renal Group's Specialised Register (to 16 January 2013) through contact with the Trials' Search Co-ordinator using search terms relevant to this review.

Selection criteria: 

We included randomised controlled trials (RCTs) of pre-emptive treatment compared with placebo, no specific treatment or with antiviral prophylaxis in solid organ transplant recipients.

Data collection and analysis: 

Four authors assessed the quality and extracted all data. Analyses used a random-effects model and results were expressed as risk ratio (RR) and 95% confidence intervals (CI).

Main results: 

We identified 15 eligible studies (1098 participants). Of these, six investigated pre-emptive treatment versus placebo or treatment of CMV when disease occurred (standard care), eight looked at pre-emptive treatment versus antiviral prophylaxis, and one reported on oral versus intravenous pre-emptive treatment.

Assessment of risk of bias identified that the processes reported for sequence generation and allocation concealment were at low risk of bias in only five and three studies, respectively. All studies were considered to be at low risk of attrition bias, and seven studies were considered to be at low risk of bias for selective reporting. Only one study reported adequate blinding of participants and personnel; no study reported blinding of outcome assessment.

Compared with placebo or standard care, pre-emptive treatment significantly reduced the risk of CMV disease (6 studies, 288 participants: RR 0.29, 95% CI 0.11 to 0.80) but not acute rejection (3 studies, 185 participants: RR 1.21, 95% CI 0.69 to 2.12) or all-cause mortality (3 studies, 176 participants: RR 1.23, 95% CI 0.35 to 4.30). Comparative studies of pre-emptive therapy versus prophylaxis showed no significant differences in preventing CMV disease between pre-emptive and prophylactic therapy (7 studies, 753 participants: RR 1.00, 95% CI 0.36 to 2.74) but there was significant heterogeneity (I² = 63%). Leucopenia was significantly less common with pre-emptive therapy compared with prophylaxis (6 studies, 729 participants: RR 0.42, 95% CI 0.20 to 0.90). Other adverse effects did not differ significantly or were not reported. There were no significant differences in the risks of all-cause mortality, graft loss, acute rejection and infections other than CMV.

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