CMV Antigenemia Directed Preemptive Prophylaxis with Oral Ganciclovir for the Prevention of CMV Disease in Liver Transplant Recipients: A Prospective, Randomized, Controlled Trial

Abstract

442 The efficacy of preemptive oral ganciclovir was compared with preemptive short-course intravenous ganciclovir for the prevention of CMV disease in 50 consecutive liver transplant recipients receiving tacrolimus as primary immunosuppression. Surveillance cultures (buffy coat for CMV pp65 antigenemia) were performed on all patients at 2, 4,6, 8, 12 and 16 weeks. Patients with positive CMV antigenemia during any surveillance culture were randomized to 2 groups (stratified by the recipient and donor CMV serostatus). The experimental group received oral ganciclovir for 6 weeks(2000 mg tid ×2 weeks, then 1000 mg tid ×4 weeks) and the standard group received 7 days of IV ganciclovir. Overall, CMV shedding (+ pp65 antigenemia) occurred in 28% (14/50) and CMV disease in 7% (1/14) of those who shed CMV. CMV disease (viral syndrome) occurred in 17% (1/6) of the patients receiving IV ganciclovir vs. 0% (0/8) receiving oral ganciclovir. None of the patients, in either study group, developed tissue invasive CMV disease. The median number of pp65 + cells/105 leukocytes, at first detection of CMV antigenemia, were 3 (range 1-9) in patients with reactivation and 18 (range 1-80) in those with primary CMV infection. CMV disease occurred in 0% (0/9) of patients with reactivation infection (5 who received oral ganciclovir and 4 who received intravenous ganciclovir). CMV viral syndrome developed in 1/5 (0/3 who received oral ganciclovir and 1/2 who received intravenous ganciclovir) in patients with primary CMV. In conclusion, preemptive prophylaxis based on CMV antigenemia can effectively target the patients for CMV prophylaxis. 72% (36/50) of the patients never received antiviral prophylaxis and did not develop CMV disease; antiviral therapy instituted upon detection of antigenemia prevented tissue invasive CMV in both ganciclovir groups. Preemptively administered oral ganciclovir appeared as effective as IV ganciclovir for the prevention of CMV disease after liver transplantation.