Clinical significance of expression of human cytomegalovirus pp67 late transcript in heart, lung, and bone marrow transplant recipients as determinedby nucleic acid sequence-based amplification

Human cytomegalovirus (HCMV) infection was monitored retrospectively by qua litative determination of pp67 mRNA (a late viral transcript) by nucleic ac id sequence-based amplification (NASBA) in a series of 50 transplant recipi ents, including 26 solid-organ (11 heart and 15 lung) transplant recipients (SOTRs) and 24 bone marrow transplant recipients (BMTRs). NASBA results we re compared with those obtained by prospective quantitation of HCMV viremia and antigenemia and retrospective quantitation of DNA in leukocytes (leuko DNAemia). On the whole, 29 patients were NASBA positive, whereas 10 were NA SBA negative, and the blood of 11 patients remained HCMV negative. NASBA de tected: HCMV infection before quantitation of viremia did but after quantit ation of leukoDNAemia and antigenemia did. In NASBA-positive blood samples, median levels of viremia, antigenemia, and leukoDNAemia were significantly higher than the relevant levels detected in NASBA-negative HCMV-positive b lood samples, By using the quantitation of leukoDNAemia as the "gold standa rd," the analytical sensitivity (47.3%), as well as the negative predictive value (68.3%), of NASBA for the diagnosis of HCMV infection intermediate b etween that of antigenemia quantitation (analytical sensitivity, 72.3%) and that of viremia quantitation (analytical sensitivity, 28.7%), while the sp ecificity and the positive predictive value were high (90 to 100%). However , with respect to the clinically relevant antigenemia cutoff of greater tha n or equal to 100 used in this study for the initiation of preemptive thera py in SOTRs with reactivated HCMV infection, the clinical sensitivity of NA SBA reached 100%, with a specificity of 68.9%. Upon the initiation of antig enemia quantitation-guided treatment, the actual median antigenemia level w as 158 (range, 124 to 580) in SOTRs who had reactivated infection and who p resented with NASBA positivity 3.5 +/- 2.6 days in advance and 13.5 (range, 1 to 270) in the group that included BMTRs and SOTRs who had primary infec tion (in whom treatment was initiated upon the first confirmation of detect ion of HCMV in blood) and who presented with NASBA positivity 2.0 +/- 5.1 d ays later. Following antiviral treatment, the durations of the presence of antigenemia and pp67 mRNA in blood wee found to he similar. In conclusion, monitoring of the expression of HCMV pp67 mRNA appears to be a promising, w ell-standardized tool fur determination of the need for the initiation and termination of preemptive therapy. Its overall clinical impact should be an alyzed in future prospective studies.