Prophylactic vs preemptive strategy for the prevention of CMV disease in solid organ transplant recipients: systematic review and meta-analysis of randomized controlled trials.

Abstract

Cytomegalovirus (CMV) is associated with significant morbidity and mortality among solid organ transplant (SOT) recipients. Strategies for CMV prevention include universal prophylaxis or preemptive approach. We aimed to evaluate the optimal approach. We performed a systematic review and meta-analysis of randomized controlled trials comparing prophylaxis versus preemptive therapy for CMV in SOT. The primary outcome was CMV disease. Subgroup analysis of outcomes in D+ R- patients was performed. Nine trials have met inclusion criteria, five of them included kidney transplant recipients, all compared val/ganciclovir universal prophylaxis versus preemptive approach. Universal prophylaxis resulted in lower probability of CMV infection (relative risk [RR] 0.44, 95% confidence interval [CI] 0.33-0.58), yet the impact on CMV disease was insignificant (RR 0.54, 95% CI 0.24-1.23), in neither SOT recipients in general nor among D+R- subgroup (RR 0.93, 95% CI 0.37-2.32). Late-onset CMV disease rates were lower with preemptive approach. Sensitivity analysis according to allocation concealment and blinding showed similar results for CMV disease. No significant differences were demonstrated for the outcomes of mortality, bacterial or fungal infection or graft related outcomes. Acute kidney injury was significantly more common with prophylaxis (RR 1.79, 95% CI 1.12-2.89). Preemptive approach is a reasonable approach for CMV prevention in SOT recipients, if feasible. Strategies for combining the preemptive with prophylaxis strategies, as well as immune monitoring, should be investigated.