A Multicenter Study of Valganciclovir Prophylaxis up to Day 120 in CMV-Seropositive Lung Transplant Recipients

Abstract

Seventy-six cytomegalovirus (CMV)-seropositive lung transplant recipients receiving valganciclovir (900 mg/day) for CMV prophylaxis were compared with a group of 87 patients receiving oral ganciclovir (3000 mg/day). Prophylaxis was administered to day 120 post-transplantation and follow-up was 1 year. In addition, a study was conducted on risk factors for CMV infection/disease. CMV disease incidence was 7.9% and 16.1% for valganciclovir and oral ganciclovir, respectively (p = 0.11). Patients receiving valganciclovir had fewer viral syndromes (2.6% vs. 11.5%, p < 0.05), a similar rate of tissue-invasive disease (5.2% vs. 4.6%, p = ns), longer time-to-onset of CMV infection/disease (197.5 vs. 155.2 days, p < 0.05), and a lower probability of infection/disease while on prophylaxis (1.3% vs. 12.6%, p < 0.01). Nonetheless, leukopenia incidence was higher with valganciclovir (15.8% vs. 2.3%, p < 0.01), as was the need for treatment withdrawal due to adverse effects (11.8% vs. 1.1%, p < 0.01). CMV infection was similar in both groups (32.9% vs. 34.5%). Induction therapy with basiliximab and glucocorticosteroid treatment were independent risk factors for developing CMV infection/disease. In conclusion, valganciclovir prophylaxis results in a low incidence of CMV disease in lung transplant recipients and appears more effective than oral ganciclovir. Despite the comparatively higher incidence of adverse events with valganciclovir, the drug can be considered safe for prophylaxis.

CMV: Prevention, Diagnosis and Therapy

“…Citations are examples supporting these statements and are not meant to include all references on this topic. Additional references can be found in the comprehensive review by Freeman (5) General indirect effects-elevated risks Bacterial infections (19,134,135) Fungal infection (19,26) Viral infections (summarized in (6)) PTLD (136) Cardiovascular events (137) New-onset diabetes mellitus after transplantation (138,139) Immunosenescence (140) Acute rejection (36,37,134) Mortality (19,134,(141)(142)(143)(144) Transplant-specific indirect effects Chronic allograft nephropathy and/or allograft loss after renal transplant (19,145,146) Accelerated hepatitis C recurrence after liver transplant (147) Hepatic artery thrombosis after liver transplant (144,148,149) Allograft vasculopathy after cardiac transplant (150,151) Bronchiolitis obliterans after lung transplant (37,141,143) hereafter referred to as D+/R−). Preemptive therapy is defined as serial testing done weekly or biweekly for the first few months after transplant or after treatment of rejection, with treatment dose antiviral therapy initiated once a certain defined positive threshold is reached.…”

Cytomegalovirus Pneumonitis Is a Risk for Bronchiolitis Obliterans Syndrome in Lung Transplantation

“…This ''late-onset CMV disease,'' often defined as disease after the prophylactic period ends, has been associated with increased risk for graft failure after kidney transplantation and increased mortality in liver transplant recipients despite adequate treatment for CMV disease once detected (8,9). Several retrospective reports have also suggested that late-onset disease occurs frequently in lung recipients despite courses of prophylaxis as long as 3-6 months (10,11).…”

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

“…Valganciclovir, an oral prodrug that achieves ganciclovir concentrations comparable to those of intravenous (i.v.) ganciclovir (11), is at least as effective and safe in reducing CMV infections after lung transplantation (8,(12)(13)(14)(15)(16)(17)(18). Controversy persists, however, over the recommended duration of valganciclovir prophylaxis.…”