Long-Term Outcomes of Pre-emptive Valganciclovir Compared with Valacyclovir Prophylaxis for Prevention of Cytomegalovirus in Renal Transplantation

Abstract

Prevention of cytomegalovirus (CMV) is essential in organ transplantation. The two main strategies are pre-emptive therapy, in which one screens for and treats asymptomatic CMV viremia, and universal antiviral prophylaxis. We compared these strategies and examined long-term outcomes in a randomized, open-label, single-center trial. We randomly assigned 70 renal transplant recipients (CMV-seropositive recipient or donor) to 3-month prophylaxis with valacyclovir (n=34) or pre-emptive valganciclovir for significant CMV viremia detected at predefined assessments through month 12 (n=36). Among the 55 patients who had a protocol biopsy specimen available at 3 years to allow assessment of the primary outcome, 9 (38%) of 24 patients in the prophylaxis group and 6 (19%) of 31 patients in the pre-emptive therapy group had moderate to severe interstitial fibrosis and tubular atrophy (odds ratio, 2.50; 95% confidence interval, 0.74-8.43; P=0.22). The prophylaxis group had significantly higher intrarenal mRNA expression of genes involved in fibrogenesis. The occurrence of CMV disease was similar in both groups, but pre-emptive therapy improved 4-year graft survival (92% versus 74%; P=0.049) as a result of worse outcomes in patients with late-onset CMV viremia. In conclusion, compared with valacyclovir prophylaxis, pre-emptive valganciclovir therapy may lead to less severe interstitial fibrosis and tubular atrophy and to significantly better graft survival.

Randomized Trial of Valganciclovir Versus Valacyclovir Prophylaxis for Prevention of Cytomegalovirus in Renal Transplantation

“…CMV viremia and disease have been shown to be independent risk factors of mortality and/or graft failure in the late renal post-transplant period (7). This association has been confirmed by studies using modern preventive strategies (8)(9)(10).…”

Impact of Antiviral Preventive Strategies on the Incidence and Outcomes of Cytomegalovirus Disease in Solid Organ Transplant Recipients

“…Current guidelines recommend both approaches, although antiviral prophylaxis is generally preferred for high-risk patients (1,2). However, direct comparison of both strategies has been assessed only in a few small randomized controlled trials (10)(11)(12)(13)(14).…”

Easier Control of Late-Onset Cytomegalovirus Disease Following Universal Prophylaxis Through an Early Antiviral Immune Response in Donor-Positive, Recipient-Negative Kidney Transplants

“…In one study directly comparing prophylactic and preemptive approaches, it was clearly demonstrated that late DNAemia occurs much more frequently in the prophylactic versus the preemptive setting (3,4). In addition, late DNAemia has been associated with poor prognosis, with a reduction in graft survival and higher patient mortality (5)(6)(7)(8)(9)(10). Moreover, it has been claimed that the preemptive strategy, usually associated with CMV DNAemia or early onset disease (EOD), may have the advantage of boosting antiviral immunity by exposure to asymptomatic DNAemia compared with universal prophylaxis (11).…”

“…Nevertheless, studies depicting the poor prognosis of LOD have rarely focused on the high-risk D+RÀ population (5) and have defined LOD as all CMV events >3 mo after transplantation including recurrences (5), which are already known to have poorer prognosis (12,13).…”