Use of Valganciclovir for Prevention and Treatment of Cytomegalovirus Disease

The development of a valine ester for ganciclovir has allowed much-improved absorption and bioavailability of oral ganciclovir and has had a significant impact on the prevention and management of cytomegalovirus infection in the immunocompromised host. Valganciclovir offers ~60% bioavailability after oral ingestion. The administration of 900 mg of valganciclovir orally is comparable to a dose of intravenous ganciclovir of 5 mg/kg, although the peak level of ganciclovir is higher than that of oral valganciclovir [ 1 ] . Given this comparability, the use of valganciclovir for preemptive therapy and even for treatment of cytomegalovirus disease is becoming quite common, even with limited comparative trial data [2]. The article by Len et al [3] from the Spanish Network for Research on Infection in Transplantation (RESITRA) in this issue of Clinical Infectious Diseases reports an observational study that offers some insight into the efficacy of valganciclovir for the prevention and treatment of cytomegalovirus disease. Although this study d sign is not as rigorous as a randomized trial, and although it was subject to some investigator and clinician bias in patient selection, the data are nevertheless compelli g and demonstrate that valganciclovir can be used for preemptive therapy for cy omegalovirus infection in organ transplant recipients [3]. The definitions of success and failure in this study are rigorous, and the number of patients studied was large. Once viral replication was established, it is quite clear that valganciclovir is effective for viral suppression, to prevent progression to cytomegalovirus syndrome or organ disease. The vast majority of the data in this study derive from kidney and liver transplant recipients (and, to a lesser extent, from heart transplant patients); therefore, generalizability of the results to lung or kidney-pancreas transplant recipients is probably not justified. Furthermore, the data provide a limited experience regarding the cytomegalovirus antibody-negative recipients of transplants from antibody-positive donors, who represent the highestrisk group for late-onset disease and relapse. Thus, additional studies are required for these groups to provide information for such use. However, I think transplant programs can feel confident that the use of valganciclovir for preemptive therapy has merit for the vast majority of organ transplant recipients. In many programs, it is already the standard of care for either prophylaxis or preemptive therapy. Although the US Food and Drug Administration has cautioned against the use of valganciclovir for prevention of cytomegalovirus infection in liver transplant recipients [4], the data here support its use and also are consistent with what many liver transplantation programs are actually using as their protocol. The data from this Spanish group are not as compelling regarding the use of valganciclovir for treatment of invasive cytomegalovirus disease, which they label "focal disease" in tables 2 and 3 of their article [3]. The success rate of 75% is less than the success rate for intravenous ganciclovir (87.5%) or intravenous ganciclovir followed by valganciclovir (96.2%). Although the difference was not statistically significant, only 8 patients with focal disease were treated exclusively with valganciclovir. Although there were only 2 treatment failures, I believe that more experience will be necessary to conclude that valganciclovir therapy is appropriate initial management of tissue invasive disease. The authors do not indicate the lo-