CMV Valganciclovir Prophylaxis Versus Preemptive Therapy after Renal Transplantation: Three Year Results of a Randomized Clinical Trial

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Background: Prophylaxis and preemptive therapy are competitive approaches to prevent cytomegalovirus (CMV) infection after renal transplantation. Several prospective randomized studies show that in high risk (D+/R-) patients, prophylaxis is the best option for preventing CMV, and that D+/R+ patients may also benefit from prophylaxis. Methods: We performed a randomized clinical trial to compare rates of CMV infection and disease of R+ renal transplant recipients receiving primary CMV prophylaxis to those treated preemptively; and whether this correlates with a higher rate of long-term graft and patient survival. Prophylaxis consisted of 900mg valganciclovir/day adjusted for renal function for 100 days post-transplantation. Patients were monitored with a quantitative CMV PCR test (Cobas® Amplicor® CMV-Monitor) and positive patients (≥ 400 copies/ml) received 1800mg/day valganciclovir adjusted for renal function followed by secondary prophylaxis with 900mg/day valganciclovir for 28 days. Three year data are summarized in this abstract. Results: 296 patients were randomized, 146 receiving prophylaxis and 150 preemptive therapy. At 3 years there were 79 acute rejections in 41 patients vs. 69 acute rejections in 44 patients in the preemptive and prophylaxis groups respectively (p=0.5940). As there were no new active CMV infections after the second year, their percentage remained significantly higher with pre-emptive therapy (38.7% vs. 11.6%, p< 0.0001). 16 of the 17 CMV infections in the prophylaxis group and 6 of the 58 in the preemptive group occurred after 100 days post transplantation. Most CMV infections and highest rate of CMV disease were seen for D+/R+ patients receiving preemptive therapy (53.9% vs. 16.7%, p< 0.0001 for CMV infections and 21.8% vs. 5.6%, p=0.0019 for CMV disease). Two additional graft losses occurred in the preemptive group (10 at 3 years) and none in the prophylaxis group (4 at 3 years) after the second year. Uncensored graft losses were twice as many in the preemptive group (n=17, 11.3%) as in the prophylaxis group (n=8, 5.5%, p=0.0702). In preemptive group patients with active CMV infection death and/or graft loss increased fourfold to 20.7% compared to patients without active CMV infection. A similar increase was not observed in the prophylaxis group (Table 1).[Table 1: Uncensored graft loss at 3 years after Tx]Conclusion: At 3 years post-transplantation, the incidence of active CMV infection in both arms did not increase, preserving the significant benefit for the prophylactic group observed at 2 years. There were twice as many graft losses and/or deaths in patients treated preemptively compared with patients who received valganciclovir prophylaxis. The ongoing study aims to determine if prophylaxis is associated with long-term benefits for R+ patients.