RANDOMIZED COMPARISON OF GANCICLOVIR AND HIGH-DOSE ACYCLOVIR FOR LONG-TERM CYTOMEGALOVIRUS PROPHYLAXIS IN LIVER-TRANSPLANT RECIPIENTS

Despite current approaches to prophylaxis, cytomegalovirus (CMV) continues to be a common cause of infection and disease in solid-organ-transplant patients. Thus, we conducted a controlled trial comparing long-term administration of ganciclovir with high-dose acyclovir for prevention of CMV infection and disease in liver transplant recipients. At the time of transplant, patients were randomised to receive either ganciclovir (6 mg/kg body weight per day intravenously from postoperative day 1 to day 30, then 6 mg/kg per day Monday through Friday until day 100) or acyclovir (10 mg/kg intravenously every 8 h from postoperative day 1 to day of discharge, then 800 mg orally four times a day until day 100). Patients were followed for development of CMV infection, CMV disease, and drug-related toxicity by frequent cultures, serological tests, laboratory measurements, and tissue biopsies. During the first 120 days after transplant, CMV infection occurred in 48 of 126 (38%) acyclovir patients but in only 6 of 124 (5%) ganciclovir patients (p<0.0001). Similarly, symptomatic CMV disease developed in 12 of 126 (10%) acyclovir patients but in only 1 of 124 (0.8%) ganciclovir patients (p=0.002). Ganciclovir reduced the incidence of CMV infection in both CMV antibody positive (37 vs 4%, p=0.001) and negative patients (42 vs 11%, p=0.06). In a multivariate analysis of donor-recipient CMV antibody status and other risk factors, prophylactic ganciclovir was the most significant factor protecting against CMV infection (p<0.0001) and disease (p=0.001). Ganciclovir and acyclovir were generally well-tolerated. Incidences of leukopenia, thrombocytopenia, renal failure, and other adverse events were similar in the two groups. CMV can be eliminated almost completely as significant pathogen in liver transplant recipients by the long-term administration of prophylactic ganciclovir. In addition, the treatment is safe.