The clinical utility of whole blood versus plasma cytomegalovirus viral load assays for monitoring therapeutic response.
BACKGROUND
In patients with cytomegalovirus (CMV) disease, regular monitoring of viral loads and treatment until negative are recommended. However, with more sensitive polymerase chain reaction (PCR) assays and cellular peripheral sample types, detection of low-level viremia is achievable. We compared a whole blood real-time PCR with a plasma PCR assay for monitoring therapeutic response.


METHODS
Patients enrolled in a trial to treat CMV disease for 21 days had regular viral load monitoring. The results of a plasma-based PCR assay were compared with a real-time PCR assay of whole blood and assessed for their ability to predict recurrence.


RESULTS
In 219 evaluable patients, viral loads in plasma versus whole blood demonstrated good correlation but significant difference in absolute value and clearance kinetics. Virus was still detectable by day 21 in 154 of 219 (70.3%) patients with the whole blood versus 105 of 219 (52.1%; P<0.001) patients with the plasma assay. The positive predictive value of persistent plasma viremia at day 21 for virologic recurrence was 41.9% vs. 36.3% for the whole blood assay. In the subset of patients with a negative plasma but positive whole blood at day 21 (n = 49), the incidence of virologic recurrence was similar to that of all patients with a negative plasma assay (23.1% vs. 23.6%).


CONCLUSIONS
When treating CMV disease, enhanced detection of residual viremia using a whole blood real-time PCR does not seem to offer significant clinical advantages nor allows for better prediction of recurrence of CMV viremia or disease. The treat-to-negative paradigm may not hold true when such assays are used.
Department of Medicine, University of Alberta, Edmonton, AB, Canada.
Luiz F
LF
Lisboa
Anders
A
Asberg
Deepali
D
Kumar
Xiaoli
X
Pang
Anders
A
Hartmann
Jutta K
JK
Preiksaitis
Mark D
MD
Pescovitz
Halvor
H
Rollag
Alan G
AG
Jardine
Atul
A
Humar
D003587:Cytomegalovirus / Q000235:genetics / Q000302:isolation & purification*; D003586:Cytomegalovirus Infections / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy / Q000821:virology*; D004279:DNA, Viral / Q000097:blood; D006801:Humans; D010949:Plasma / Q000821:virology; D016133:Polymerase Chain Reaction / Q000379:methods; D011237:Predictive Value of Tests; D012008:Recurrence; D019737:Transplants / Q000009:adverse effects; D016896:Treatment Outcome; D019562:Viral Load / Q000379:methods*; D014766:Viremia / Q000097:blood / Q000175:diagnosis / Q000821:virology
D004279:DNA, Viral