Following Universal Prophylaxis with Intravenous Ganciclovir and Cytomegalovirus Immune Globulin, Valganciclovir is Safe and Effective for Prevention of CMV Infection Following Lung Transplantation

Abstract

We prospectively determined the safety and efficacy of valganciclovir for prevention of cytomegalovirus (CMV) in at-risk (donor positive/recipient negative [D+/R−] or R+) lung transplant recipients. We also determined the length of prophylaxis required to significantly decrease both CMV infection and disease. Consecutive lung transplant recipients surviving >30 days (n = 90) received combination prophylaxis with intravenous (i.v.) ganciclovir (GCV) 5 mg/kg/day and cytomegalovirus immune globulin (CMV-IVIG) followed by valganciclovir (450 mg twice-daily) to complete 180, 270 or 365 days of prophylaxis. This group was compared to a historical group (n = 140) who received high-dose oral acyclovir following i.v. GCV and CMV-IVIG. CMV disease was significantly lower in patients receiving valganciclovir compared to acyclovir (2.2% vs. 20%; p < 0.0001). Freedom from CMV infection and disease was significantly greater (p < 0.02) in patients receiving 180, 270 or 365 days of prophylaxis (90%, 95% and 90%, respectively) compared to those receiving 100-179 days (64%) or <100 days (59%). No patient receiving valganciclovir died during the study. Following prophylaxis with i.v. GCV and CMV-IVIG, valganciclovir is safe and effective for prevention of CMV infection and disease in at-risk lung transplant recipients. The required length of prophylaxis was at least 180 days.

Ganciclovir-Resistant Cytomegalovirus Infections among Lung Transplant Recipients Are Associated with Poor Outcomes despite Treatment with Foscarnet-Containing Regimens

“…The optimal preventive regimen against CMV infection following lung transplantation remains undefined, but most programs employ universal antiviral prophylaxis (2). Most prophylaxis studies in lung transplant recipients have employed ganciclovir, alone or in combination with CMV hyperimmunoglobulin G (3)(4)(5)(6)(7)(8)(9)(10). Valganciclovir, an oral prodrug that achieves ganciclovir concentrations comparable to those of intravenous (i.v.)…”

Low-Dose Valganciclovir for CMV Prophylaxis after Lung Transplantation

“…e optimal duration of CMV prophylaxis is unknown, but in general, the longer the duration of prophylaxis, the lower the incidence of primary or recurrent CMV disease. is has been demonstrated in kidney transplant recipients aer six months of CMV prophylaxis with valganciclovir [19], and in recent studies by Humar and Zamora et al [20,21], it has been demonstrated that a longer duration of prophylaxis is bene�cial. However, it is not clear how much exposure to ganciclovir is required for effective prophylaxis.…”

“…Different centers have varying dosages, drugs, and regimens for CMV prophylaxis, which makes comparison between different reported results difficult with some using IV ganciclovir, CMV immune globulins, and valganciclovir in different combinations and varying lengths of time. Recently Zamora et al [21] evaluated valganciclovir for CMV prophylaxis in lung transplant recipients. All patients received 30 days of IV ganciclovir and three doses of CMV immune globulin (if R+) or 90 days of IV ganciclovir with seven doses of CMV immune globulin (if D+R−).…”

Valganciclovir: Recent Progress

“…Thus empiric trials of extended prophylaxis in a D+/R− renal (7) and any-risk lung (8) (14,15). There were no differences in AUC between liver, kidney and heart recipients.…”