Clinical significance of post‐prophylaxis cytomegalovirus infection in lung transplant recipients

Abstract

Cytomegalovirus (CMV) disease has been associated with the development of chronic lung allograft dysfunction (CLAD) after transplantation. However, the relevance of CMV replication occurring after the discontinuation of antiviral prophylaxis on the development of CLAD has not been fully established. Patients who underwent lung transplantation during 2004-2014 were included. All patients received antiviral prophylaxis for 3-6 months, followed by monitoring of CMV replication during the first year post-transplantation (preemptive therapy). Risk factors for the development of CLAD were assessed by Cox models. A linear regression model with an interaction coefficient between time and CMV infection was used to evaluate the influence of CMV infection on the evolution of FEV . Overall, 69 patients were included, 30/69 (43%) patients developed at least 1 episode of significant CMV infection, and 8/69 (11.5%) patients developed CMV disease. After a median follow-up of 3.67 years, 25/69 (36%) patients developed CLAD and 14/69 (20%) patients died. In the univariate Cox analysis, significant CMV infection (HR 1.177, P = .698), CMV disease (HR 1.001, P = .998), and duration of CMV replication (HR 1.004, P = .758) were not associated with CLAD. Only bacterial pneumonia tended to be associated with CLAD in the multivariate model (HR 2.579, P = .062). We did not observe a significant interaction between CMV replication and evolution FEV (interaction coefficient 0.006, CI 95% [-0.084 to 0.096], P = .890). In this cohort of lung transplant recipients receiving antiviral prophylaxis and monitored by preemptive therapy post-prophylaxis, CMV infection did not have impact on long-term allograft lung function.

Extending cytomegalovirus prophylaxis in high‐risk (D+/R−) lung transplant recipients from 6 to 9 months reduces cytomegalovirus disease: A retrospective study

“…Palmer et al 28 found no differences in overall BOS development. This was corroborated in a recent study of the Swiss cohort showing no impact of CMV on CLAD 29 . We must interpret our data with caution, as CLAD usually develops later in the course of post‐transplant.…”

“…This was corroborated in a recent study of the Swiss cohort showing no impact of CMV on CLAD. 29 We must interpret our data with caution, as CLAD usually develops later in the course of post-transplant. Since our latest patient included was transplanted in December 2017, we were unable to do analyses of CLAD incidence beyond one year after transplantation.…”

Viral infections in lung transplantation

“…Those immunomodulatory effects of CMV may predispose patients to opportunistic infections, in particular fungal infections (101,108,109). The use of universal antiviral prophylaxis in the current era seems to reduce the impact of CMV in allograft outcomes (110,111).…”

“…Without a preventive strategy, CMV infection and disease typically occur during the first three months after transplantation (93). Current incidence of CMV disease in lung transplant recipients varies from 5% to 40% depending on serological status and preventive strategy used (111)(112)(113). The main preventive strategies against CMV disease are antiviral prophylaxis and preemptive approach.…”

Chronic Lung Allograft Dysfunction: Evolving Concepts and Therapies

“…In a cohort of lung transplant recipients who received CMV prophylaxis for 3 to 6 months, followed by monitoring and preemptive therapy, neither CMV infection nor CMV disease had a significant impact on long-term allograft lung function. 246 Community-acquired respiratory viruses (CARVs) have also been implicated in CLAD, especially in patients who develop lower respiratory tract infections. 80 In one observational study that categorized viral infections based on the presence or absence of pneumonia, only those with pneumonia had an increased risk for CLAD.…”