PROPHYLAXIS OF CYTOMEGALOVIRUS-INFECTION IN LIVER-TRANSPLANTATION - ARANDOMIZED TRIAL COMPARING A COMBINATION OF GANCICLOVIR AND ACYCLOVIRTO ACYCLOVIR

Background The optimal prophylactic regimen to prevent cytomegalovirus (CMV) infection and disease in orthotopic liver-transplant patients r emains to be established. We tested whether a combination of intraveno us ganciclovir (GCV) followed by high dosages of oral acyclovir (ACV) for 4 months provided a higher degree of protection from CMV than oral ACV alone. Methods. One hundred sixty-seven liver-transplant recipien ts were randomized to receive 120 days of antiviral treatment starting at the time of transplantation consisting of either ACV 800 mg orally four times daily (n=84) or 14 days of GCV 5 mg/kg intravenously every 12 hr followed by oral ACV 800 mg four times daily (n=83). Prospectiv e laboratory and clinical surveillance was performed to determine prim ary endpoints (onset of CMV infection and CMV disease) and secondary e ndpoints (rates of fungal and bacterial infection, allograft rejection , and survival after transplantation). One-year event rates are presen ted as cumulative percentages. Results. During the first year after tr ansplantation, CMV infection developed in 57% of patients treated with ACV and in 37% of patients treated with GCV + ACV (P=0.001). CMV dise ase developed in 23% of patients treated with ACV and in 11% of patien ts treated with GCV + ACV (P=0.03). In seronegative recipients of allo grafts from CMV-seropositive donors (D+/R-), CMV disease developed in 58% of patients treated with ACV and in 25% of patients treated with G CV + ACV (P=0.04). In the D+/R- group, 54% of patients treated with AC V and 17% of patients treated with GCV + ACV developed infection with Candida albicans (P=0.05). Conclusions. Prophylaxis of CMV infection i n liver-transplant patients with 14 days of intravenous GCV followed b y high-dosage oral ACV is more effective than high-dosage oral AGV alo ne at reducing CMV infection and disease, even for patients in the D+/ R- cMV serological group.