Comparison of HHV-6 DNA detection in plasma and whole blood in allogeneic hematopoietic stem cell transplant recipients: frequent false-positive results for active HHV-6 infection using whole blood samples

In this prospective observational study, we compared the human herpesvirus-6 (HHV-6) DNA load in serially collected paired plasma and whole blood (WB) samples from allogeneic hematopoietic stem cell transplantation (HSCT) recipients. A total of 721 paired samples were collected from 68 recipients. The positive rate for HHV-6 DNA was 9.7 and 35.0% in plasma and WB samples, respectively (P<0.001). The correlation of HHV-6 DNA load between plasma and WB was poor (R-2=0.250). After reaching peak levels, HHV-6 DNA showed a delayed decrease in WB in comparison with plasma (median, 28 versus 7days, P<0.001). We additionally tested HHV-6 mRNA status in 95 samples from eight patients. To identify positive HHV-6 mRNA, plasma HHV-6 DNA showed 55.0% sensitivity and 100% specificity, whereas WB HHV-6 DNA showed 90.0% sensitivity and 68.0% specificity. The false-positive rate for identifying positive HHV-6 mRNA was 0% for plasma HHV-6 DNA and 32.0% for WB HHV-6 DNA. Although WB was more sensitive than plasma for detecting HHV-6 reactivation, the rates of false positivity for active HHV-6 infection were higher for WB than for plasma.