Relationship between pp65 antigenemia levels and real-time quantitative DNA PCR for Human Cytomegalovirus (HCMV) management in immunocompromised patients.

Background: Quantitative real-time PCR assays, which are more rapid and practical than pp65
antigenemia determination, are progressively becoming the preferred method for monitoring
Human Cytomegalovirus (HCMV) reactivation. However, the relationship between HCMV DNA
and antigenemia levels is still under investigation. The aim of this study was to analyse the
relationship between HCMV DNA and pp65 antigenemia levels in order to identify clinically useful
threshold values for the management of patients.
Methods: 475 consecutive samples from 156 immunosuppressed patients were tested for HCMV
by pp65 antigenemia and Real-time PCR assay.
Results : 136 out of 475 consecutive samples derived from 48 patients showed evidence of HCMV
infection. HCMV DNA was detected in 106 samples, pp65 antigen in 3, and both markers in 27.
pp65 antigen detection was associated with higher HCMV DNA levels. The cut-off HCMV DNA
level that best predicted pp65 antigenemia in this series of samples was 11,500 copies/ml, but
different threshold levels could be observed for specific groups of patients. HCMV disease was
observed in 5 out of 48 patients with active HCMV infection. The presence of clinical symptoms
was associated with positive pp65 and with higher antigenemia levels. Higher HCMV DNA load at
the onset of viral replication was correlated to the development of clinical symptoms.
Conclusion: Both pp65 antigenemia and HCMV DNA load can be useful for the prospective
monitoring of immunocompromised subjects. Specific cut-off levels capable of triggering
preemptive antiviral treatment should be determined in accordance to the type of test used and
the characteristics of patients and prospectively validated.