Clinical significance of asymptomatic cytomegalovirus viremia in lung transplant recipients receiving universal antiviral prophylaxis


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A Master's thesis.
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Master (thesis) (master)
Clinical significance of asymptomatic cytomegalovirus viremia in lung transplant recipients receiving universal antiviral prophylaxis
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Université de Lausanne, Faculté de biologie et médecine
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Background: Cytomegalovirus (CMV) disease has been associated with the development of chronic lung allograft dysfunction (CLAD) after lung transplantation. However, the relevance of asymptomatic CMV viremia occurring after the discontinuation of antiviral prophylaxis (late-onset CMV replication) on the development of CLAD is not fully understood. We aimed to assess the long- term clinical impact of asymptomatic CMV replication in a cohort of lung transplant recipients receiving universal antiviral prophylaxis.
Methods: We performed a single-center study including all patients who underwent lung transplantation between 2004 and 2014. Patients received valganciclovir prophylaxis for 3 to 6 months (according to CMV serostatus risk of the donor [D] and recipient [R]), followed by monitoring of CMV replication by PCR during the first year post transplant. CLAD was defined according to ISHLT definitions. Risk factors for the development of CLAD and for mortality were assessed by univariate and multivariate Cox models. A lineal regression model was used to evaluate the influence of CMV replication in the evolution of FEV1.
Results: Overall, 69 patients were included. CMV serostatus was D-/R- in 13 (19%) patients, D-/R+ in 17 (25%) patients, D+/R+ in 27 (39%) patients and D+/R- in 12 (17%) patients. Overall, 34/69 (49%) patients developed at least one episode of asymptomatic CMV replication and 8/69 (11.5%) patients developed CMV disease. Median duration of CMV replication in viremic patients was 57.5 days. After a median follow-up of 3.69 years, 25/69 (36%) patients developed CLAD and 14/69 (20%) patients died. In the univariate cox analysis, bacterial pneumonia was associated with a higher incidence of CLAD (HR 2.58, p=0.06), but asymptomatic CMV replication (HR 1.36, p=0.45), CMV disease (HR 1.00, p=0.99), and duration of CMV replication (HR 1.00, p=0.76) were not. In the multivariate model, bacterial pneumonia remained associated with CLAD (HR 2.53, p=0.06). In the mixed model of linear regression, we did not observe a correlation between CMV replication and a significant decline of FEV1 (estimate -0.162, CI 95% [-0.498 to 0.170], p=0.35). CMV replication was not associated with a higher mortality (HR 0.75, p=0.62).
Conclusion: In this cohort of lung transplant recipients receiving antiviral universal prophylaxis, asymptomatic CMV replication did not influence long-term allograft lung function and patient survival. These results suggest that the use of universal prophylaxis is protective against the indirect effects of CMV, irrespective of the development of late-onset CMV replication.
viral infection, chronic lung allograft dysfunction, lung transplantation, outcomes
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01/09/2016 8:54
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20/08/2019 13:30
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