Valganciclovir Prophylaxis Versus Preemptive Therapy in Cytomegalovirus-Positive Renal Allograft Recipients: 1-Year Results of a Randomized Clinical Trial

Background. Cytomegalovirus (CMV) prevention can be achieved by prophylaxis or preemptive therapy. We performed a prospective randomized trial to determine whether renal transplant recipients with a positive CMV serostatus (R+) had a higher rate of CMV infection and disease after transplantation when treated preemptively for CMV infection, compared with primary valganciclovir prophylaxis. Methods. Prophylaxis was 2X450 mg oral valganciclovir/day for 100 days; preemptive patients were monitored by CMV-polymerase chain reaction (PCR), and after a positive PCR test received 2X900 mg valganciclovir/day for at least 14 days followed by secondary prophylaxis. Valganciclovir dosage was adjusted according to renal function. Patients are followed up for 5 years and initial 12-month data are presented. Two hundred and ninety-six recipients were analyzed (168 donor/recipient seropositive [D+/R+], 128 donor seronegative/recipient seropositive [D-/R+]; 146 receiving prophylaxis and 150 preemptive therapy). Results. Overall, CMV infection (asymptomatic CMV viral load >= 400 CMV DNA copies/mL proven by CMV-PCR) was significantly higher in recipients under preemptive therapy (38.7% vs. 11.0%, P<0.0001), with the highest incidence in D+/R+ preemptive patients (53.8% vs. 15.6%, P<0.0001). D+/R+ recipients with preemptive therapy also had the highest rate of CMV disease (CMV syndrome and tissue-invasive disease that was clinically diagnosed and biopsy proven) (19.2% vs. 4.4%, P = 0.003). Renal function assessed by creatinine clearance was similar for both groups. Graft loss occurred in 7 vs. 4 patients on preemptive versus prophylactic therapy (P > 0.05). Tolerability was similar for both treatment groups. Conclusions. Oral valganciclovir prophylaxis significantly reduces CMV infection and disease, particularly for D+/R+ patients. Hence, our study supports routine prophylaxis for all D+/R+ recipients.