Pre-emptive Treatment for Cytomegalovirus Viremia to Prevent Cytomegalovirus Disease in Solid Organ Transplant Recipients

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Abstract
Background. Cytomegalovirus (CMV) is a significant cause of morbidity and mortality in solid organ transplant recipients. Preemptive treatment with antiviral agents of patients with CMV viremia has been widely adopted as an alternative to routine prophylaxis to prevent CMV disease. This study was conducted to evaluate the efficacy of pre-emptive treatment in preventing symptomatic CMV disease. Methods. The Cochrane CENTRAL Registry, MEDLINE, EMBASE, and reference lists were searched for randomized trials of preemptive treatment in solid organ transplant recipients. Two authors extracted all data; analysis was with a random effects model and results expressed as relative risk (RR) and 95% confidence intervals (CI). Results. Ten eligible trials (476 patients) were identified, six of preemptive treatment versus placebo or standard care (treatment of CMV when disease occurred), three of preemptive treatment versus antiviral prophylaxis and one of oral versus intravenous preemptive treatment. Compared with placebo or standard care, preemptive treatment significantly reduced the risk of CMV disease (6 trials, 288 patients, RR 0.29, 95% CI 0.11 to 0.80) but not acute rejection (3 trials, 185 patients, RR 1.06, 95% CI 0.64 to 1.76) or all-cause mortality (2 trials, 176 patients, RR 1.23, 95% CI 0.35 to 4.30). Comparative trials of preemptive therapy versus prophylaxis showed no significant difference in the risks of CMV disease (2 trials, 151 patients, RR 0.42, 95% CI 0.07 to 2.65), acute rejection (1 trial, 70 patients, RR 0.94, 95% CI 0.42 to 2.09) or all-cause mortality (3 trials, 151 patients, RR 1.86, 95% CI 0.61 to 5.72). Conclusions. Few randomized trials have evaluated the effects of preemptive therapy to prevent CMV disease. Preemptive therapy is effective compared with placebo or standard care, but additional head-to-head trials are required to determine the relative benefits and harms of preemptive therapy and prophylaxis to prevent CMV disease in solid organ transplant recipients.