PREEMPTIVE GANCICLOVIR THERAPY TO PREVENT CYTOMEGALOVIRUS DISEASE IN CYTOMEGALOVIRUS ANTIBODY-POSITIVE RENAL-TRANSPLANT RECIPIENTS - A RANDOMIZED CONTROLLED TRIAL

Objective: To determine whether preemptive ganciclovir therapy adminis tered daily during antilymphocyte antibody therapy can prevent cytomeg alovirus disease in renal transplant recipients who are positive for c ytomegalovirus antibody.Design: Randomized, controlled, multicenter tr ial. Setting: 6 university-affiliated transplantation centers. Patient s: 113 renal transplant recipients who were positive for cytomegalovir us antibody. Intervention: Patients were randomly assigned to receive either 1) ganciclovir, 2.5 mg/kg body weight administered intravenousl y on every day that antilymphocyte antibody therapy was administered o r 2) no anticytomegalovirus therapy. Measurements: Patients were obser ved for 6 months after completion of antilymphocyte antibody therapy f or development of cytomegalovirus disease and cytomegalovirus viremia. Results: Cytomegalovirus disease occurred in 14% of patients (9 of 64 ) who received preemptive ganciclovir therapy and in 33% of controls ( 16 of 49) (P = 0.018). Cytomegalovirus was isolated from buffy-coat sp ecimens from 17% of patients (11 of 64) receiving preemptive ganciclov ir and from 35% of controls (17 of 49) (P = 0.03). Controlling for the reason (induction or treatment of rejection) for using antilymphocyte antibodies in a Cox proportional hazards model, we found that preempt ive ganciclovir still protected against cytomegalo-virus disease (adju sted relative risk, 0.27; 95% CI, 0.12 to 0.64). No adverse events wer e attributed to preemptive ganciclovir therapy during or within 6 mont hs of its administration. Conclusions: Preemptive ganciclovir therapy administered daily during courses of treatment with antilymphocyte ant ibodies reduced the excessive occurrence of cytomegalovirus disease in renal transplant recipients who were positive for cytomegalovirus ant ibody. This approach, which links the most potent immuno-suppression t o intensive antimicrobial therapy, allows preventive therapy to be giv en to those patients at greatest risk for developing infectious compli cations. These patients are likely to benefit most from the preventive strategy.