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Clinical Utility of Cytomegalovirus Cell-Mediated Immunity in Transplant Recipients With Cytomegalovirus Viremia

Lisboa, Luiz F.1,2,3; Kumar, Deepali1,2; Wilson, Leticia E.1,2; Humar, Atul1,2

doi: 10.1097/TP.0b013e31823c1cd4
Clinical and Translational Research

Background. A CD8+ T-cell response to cytomegalovirus (CMV) has been associated with control of viral replication. Assessment shortly after the onset of asymptomatic viremia could help significantly refine preemptive strategies.

Methods. We conducted a prospective study of organ transplant recipients who developed asymptomatic low-level viremia not initially requiring antiviral therapy. Cell-mediated immunity (CMI) was measured shortly after viremia onset and longitudinally using the Quantiferon-CMV assay. The primary outcome was the ability to predict spontaneous clearance versus virologic and/or clinical progression.

Results. We enrolled 42 transplant patients, of which 37 were evaluable. Viral load at onset was 1140 copies/mL (interquartile range 655–1542). Spontaneous viral clearance occurred in 29 of 37 (78.4%) patients and 8 of 37(21.6%) had clinical and/or virologic progression requiring antivirals. At baseline, a positive CMI test (interferon-γ≥0.2 IU/mL) was present in 26 of 37(70.3%) patients. In patients with a positive CMI, the incidence of subsequent spontaneous viral clearance was 24 of 26 (92.3%) compared with 5 of 11 (45.5%) in patients with a negative CMI at onset (P=0.004). The absolute interferon-γ production was higher in patients with spontaneous clearance versus progression at all time points tested. Analysis of different cutoffs for defining a positive test suggested that the best threshold was 0.1 or 0.2 IU/mL of interferon-γ.

Conclusions. CMI assessment shortly after the onset of CMV viremia may be useful to predict progression versus spontaneous viral clearance, thereby helping guide the need for antiviral therapy and refining current preemptive strategies.

1Transplant Infectious Diseases, Department of Medicine, University of Alberta, Edmonton, Canada.

2Li Ka Shing Institute of Virology, University of Alberta, Edmonton, Canada.

D.K. and A.H. are recipients of research funding from Hoffman-La Roche, for studies unrelated to the present article. The authors declare no conflicts of interest.

The Quantiferon-CMV kits were provided by Cellestis International but Cellestis International had no role in the study concept, design, data collection, analysis, manuscript writing and did not review the data or manuscript before submission for publication.

Address correspondence to: Luiz F. Lisboa, M.D., Transplant Infectious Diseases, Li Ka Shing Institute of Virology, University of Alberta, 6-030 Katz Building, Edmonton, AB, Canada T6G 2E1. E-mail:

All the authors participated in study design and critical review of the manuscript. L.F.L. and L.E.W. participated in patient enrollment. L.F.L., D.K., and A.H., participated in data analysis and manuscript writing.

Received 21 July 2011. Revision requested 17 August 2011.

Accepted 7 October 2011.

© 2012 Lippincott Williams & Wilkins, Inc.