A Trial of Valganciclovir Prophylaxis for Cytomegalovirus Prevention in Lung Transplant Recipients

Cytomegalovirus (CMV) remains an important cause ofmorbidity and mortality in lung transplant recipients and issecond only to bacteria as the most common opportunis-tic pathogen (1,2). In fact, the rate of CMV infection anddisease in lung transplantation is higher than in other solidorgan transplant groups. Lung and heart–lung recipientswho are not receiving antiviral prophylaxis have a reportedincidence of CMV disease ranging from 38–75% (2). Inva-sion of the allograft resulting in CMV pneumonitis is notuncommon and may result in substantial mortality. In ad-dition to directly attributable effects, CMV may also havean immunomodulatory effect in transplant recipients, andactive CMV disease has been found to be an independentrisk factor for the development of other infectious com-plications such as bacteremia, invasive fungal disease andEpstein-Barr virus related posttransplant lymphoprolifera-tive disease (3–5). In addition, CMV may be an importantrisk factor for the development of bronchiolitis obliteranssyndrome(BOS)postlungtransplant(6,7).Giventhepoten-tial for adverse consequences of CMV, strategies aimedat preventing the development of active infection arepreferable.One option for the prevention of CMV in lung transplant re-cipients is to use prolonged ganciclovir (either intravenousor oral) prophylaxis with or without immune globulin (8).However, oral ganciclovir has a low bioavailability necessi-tatingthreetimesadaydosingtoachieveadequateplasmalevels. In addition, concern exists regarding the develop-ment of antiviral resistance due to suboptimal ganciclovirlevels achieved with oral ganciclovir (9). Oral valgancicloviris an oral prodrug of ganciclovir that is rapidly hydrolyzedto ganciclovir after oral ingestion. It has a bioavailabilityof about 60% compared to 6–9% for standard oral ganci-clovir (10). Many lung transplant programs have adoptedvalganciclovir as an alternate to prolonged courses of in-travenous or oral ganciclovir. We prospectively assessedvirologic and clinical outcomes using a 3-month course ofvalganciclovirprophylaxisinlungtransplantrecipientscom-pared with standard ganciclovir prophylaxis.