Cytomegalovirus DNA Load Patterns Developing After Lung Transplantation Are Significantly Correlated With Long-Term Patient Survival

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Abstract
Cytomegalovirus (CMV) causes complications after lung transplantation (LuTX). We have investigated whether patient survival is associated with CMV DNA load patterns developing in EDTA-plasma and bronchoalveolar lavage (BAL) during the first year after LuTX and whether patients' predispositions influence this development. CMV DNA loads in plasma and BAL were investigated serially in 84 LuTX recipients. Various patient characteristics and variants in mannose-binding lectin and toll-like receptor 2 genes were analyzed. Patient survival beyond 1 year posttransplantation and influence of patient-specific factors on viral load development were assessed by Kaplan-Meier survival and Cox regression methods. Four distinct group patterns were observed: (a) less than 1000 copies CMV DNA/mL in plasma and BAL (42%); (b) more than 1000 copies/mL in BAL only (21%); (c) one limited episode (25%), or (d) more than one episode of more than 1000 copies/mL plasma (12%). The risk of death after the first year was elevated 14-fold in group D and sixfold in group B. CMV DNA load patterns were not associated with patient-specific factors except CMV-D+/R- status. Initial and peak plasma CMV DNA levels were significantly increased in group D. Active CMV replication that is not limited after one episode of CMV DNAemia leads to significantly decreased long-term survival after LuTX.