Prevention of Cytomegalovirus Infection and Disease After Lung Transplantation: Results Using a Unique Regimen Employing Delayed Ganciclovir

Abstract

Many lung transplant programs employ lengthy regimens of IV ganciclovir therapy to prevent disease due to cytomegalovirus (CMV). In 1994, we introduced a regimen of delayed ganciclovir prophylaxis for CMV infection. This consisted of 2 weeks of IV ganciclovir therapy, initiated 3 to 4 weeks after transplantation, with subsequent viral monitoring and preemptive therapy as needed. When not receiving ganciclovir, patients received oral acyclovir, 800 mg tid, for 6 months. CMV-seronegative patients with seropositive donors also received four doses of CMV hyperimmune globulin. This study analyzes the CMV outcomes of 54 patients who received the delayed regimen compared to 33 historical control subjects who received only acyclovir prophylaxis (n = 28) or oral acyclovir and 2 to 4 weeks of ganciclovir early after transplantation (n = 5). CMV detection was by shell vial culture or IgG seroconversion; after 1996, CMV detection was by blood antigenemia. The diagnosis of CMV disease also required a typical clinical syndrome or pathologic evidence of CMV. The main outcome was the actuarial incidence of CMV infection and disease. In order to account for the effect of other important risk factors for CMV infection, the time to CMV infection and disease was also studied as dependeant variables in a Cox proportional-hazard analysis, with the delayed regimen and other important risk factors as independent variables. The delayed regimen reduced the actuarial incidence of CMV infection from 80 to 48% (p < 0.001) and CMV disease from 31 to 10% (p < 0.01). No seropositive patient receiving the delayed regimen developed CMV disease. Twelve of the 54 patients in the study group required additional IV antiviral treatment, but the total use of ganciclovir averaged only 18 days per patient. In a Cox proportional-hazards model, the use of delayed ganciclovir was the only factor that showed a significant association with freedom from CMV infection (hazard ratio [HR], 0.43; 95% confidence interval [CI], 0.24 to 0.75; p = 0.003) and CMV disease (HR, 0.29; 95% CI, 0.10 to 0.86; p = 0.03). A regimen of CMV prophylaxis employing 2 weeks of IV ganciclovir initiated 3 to 4 weeks after lung transplantation followed by virologic monitoring and preemptive therapy as needed provides good protection against CMV disease.