We examined the detection of low-level viraemia at week 24 as a predictor of sustained virological response (SVR) and viral relapse/breakthrough, and the agreement between the Roche Cobas TaqMan™ HCV RNA assay (TaqMan) and Roche Cobas® Amplicor HCV qualitative assay (Amplicor; both Roche Molecular Diagnostics, Pleasanton, CA, USA) for detection of low-level viraemia.
Methods
A total of 871 treatment-naive HCV genotype 1 patients participating in an induction-dose pegylated interferon therapy study had virological responses assessed using TaqMan. A total of 151 patients with HCV RNA levels ≤500 IU/ml had samples tested in parallel using the Amplicor and TaqMan assays.
Results
SVR was significantly lower and relapse/breakthrough significantly higher in patients with low-level residual viraemia at week 24 compared with those who had undetectable viraemia: SVR was 72%, 29% and 14% (P<0.0001) and relapse/breakthrough 28%, 71% and 86% (P<0.0001) in patients with viraemia that was undetectable, detectable <15 IU/ml and detectable 15–<50 IU/ml, respectively, at week 24. The negative predictive value (NPV) for a week-24 virological response for SVR was 86%, 90% and 90% using Taq-Man cutoffs of undetectable, <15 IU/ml and <50 IU/ml, respectively. The percentage agreement between Amplicor and TaqMan was similarly high for TaqMan cutoffs of 50 IU/ml and 15 IU/ml, but lower for undetectable viraemia (83%, 83% and 70%, respectively).
Conclusions
These data emphasize the importance of achieving undetectable HCV RNA during pegylated interferon therapy to maximize SVR; however, the current 24-week stopping rule of undetectable HCV RNA appears too stringent when using sensitive PCR assays given the observed lower NPV for SVR using the Taq-Man undetectable cutoff. Our data also suggest that a TaqMan <15 IU/ml result is comparable to an Amplicor-negative result (that is, below the assay cutoff value) when monitoring viral response.
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