Human cytomegalovirus pp67 mRNAemia versus pp65 antigenemia for guiding preemptive therapy in heart and lung transplant recipients: a prospective, randomized, controlled, open-label trial.
BACKGROUND
Preemptive therapy of human cytomegalovirus (HCMV) infections has gained popularity in transplantation centers. However, standardized protocols are not available. In particular, whether a qualitative molecular assay for detection of a late (pp67) HCMV mRNA represents a valuable alternative to quantitative antigenemia remains to be defined.


METHODS
Overall, 82 heart (HTR) and lung (LTR) transplant recipients were randomized into two arms, where therapy was guided by qualitative pp67 mRNA NASBA (40 patients) or quantitative antigenemia (42 patients). In the NASBA arm, both primary and recurrent infections were treated upon first confirmed positive NASBA result. In the antigenemia arm, primary infections were treated upon first confirmed positive result, while recurrent infections were treated upon cutoff of 100 pp65-positive leukocytes. In both arms, therapy was stopped upon virus disappearance. Primary endpoint was duration of therapy.


RESULTS
The number of treated/infected patients was significantly higher in the NASBA arm (25/30 vs. 15/39; P=0.015), as was the number of treated/relapsing patients (5/8 vs. 1/11; P=0.040), whereas the number of HCMV-infected/total number of patients was significantly higher in the antigenemia arm (39/42 vs. 30/40; P=0.026). Thus, in the NASBA arm, although the median duration of therapy was shorter compared to antigenemia (17 vs. 21 days, P>0.05), the overall number of days of therapy was significantly higher. No patient developed HCMV disease.


CONCLUSIONS
pp67 mRNA NASBA can safely replace antigenemia, with some apparent advantages (semiautomation and objectivity of test results) and disadvantages (overtreatment of patients and greater duration of overall treatment).
Gerna
Giuseppe
G
Servizio di Virologia, IRCCS Policlinico San Matteo, 27100 Pavia, Italy. g.gerna@smatteo.pv.it
Baldanti
Fausto
F
Lilleri
Daniele
D
Parea
Maurizio
M
Torsellini
Maria
M
Castiglioni
Barbara
B
Vitulo
Patrizio
P
Pellegrini
Carlo
C
Viganò
Mario
M
Grossi
Paolo
P
Revello
Maria Grazia
MG
D000328:Adult; D003586:Cytomegalovirus Infections / Q000453:epidemiology / Q000503:physiopathology / Q000517:prevention & control* / Q000821:virology; D005260:Female; D016041:Heart-Lung Transplantation; D006801:Humans; D015994:Incidence; D007700:Kinetics; D008297:Male; D010750:Phosphoproteins / Q000097:blood* / Q000235:genetics*; D012333:RNA, Messenger / Q000097:blood*; D012367:RNA, Viral / Q000097:blood*; D019562:Viral Load; D014763:Viral Matrix Proteins / Q000097:blood* / Q000235:genetics*
D010750:Phosphoproteins; D012333:RNA, Messenger; D012367:RNA, Viral; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa; C464963:pp67 protein, human cytomegalovirus