Comparison of three quantitative HCV RNA assays in samples from HCV genotype 1- or 4-infected patients treated with the NS3/4A protease inhibitor simeprevir

• Differences between HCV RNA assays might influence treatment decisions.
• Concordance of 3 real-time PCR-based HCV RNA assays was tested.
• Plasma samples from Phase III simeprevir/PegIFN/RBV studies (HCV genotype 1 and 4) were used.
• Inter-assay concordance was generally good, except in low viremic samples at early time points.
• An HCV RNA threshold <25 IU/mL was more assay-independent than RNA undetectability.

BackgroundMonitoring HCV RNA levels during treatment is an important tool for managing protease-inhibitor-based regimens, and different assays used in clinical practice can impact treatment decisions.ObjectivesThe concordance of three HCV RNA assays was determined, and their impact on treatment decisions assessed using samples from HCV genotype (GT) 1- and GT4-infected patients treated with the NS3/4A inhibitor simeprevir in combination with pegylated interferon-α/ribavirin.Study designPlasma samples collected during the simeprevir Phase III studies QUEST-1 and QUEST-2 (GT1), and RESTORE (GT4) were analyzed with the Roche High-Pure-System COBAS® TaqMan® HCV v2.0 (HPS), the Roche AmpliPrep COBAS® TaqMan® HCV v2.0 (CAP), and the Abbott RealTime HCV (ART) assay.ResultsIn GT1, of the 440 samples, 81% were undetectable (rapid virological response; RVR) by HPS at Week 4, 76% by CAP and 44% by ART. In GT4 (103 samples), RVR rates were 67% by HPS and 24% by ART. HCV RNA <25 IU/mL at Week 4 was observed for 95–96% and 92% GT1 samples and 86% and 74% GT4 samples by HPS/CAP and ART, respectively. At Week 12, assay concordance for undetectability was high in GT1 and GT4, (95–98% and 93%, respectively).ConclusionsWhile different HCV RNA assays can lead to substantially different RVR rates, a good concordance was observed with a cut-off of 25 IU/mL. Sustained virologic response rates among GT1 patients achieving RVR or <25 IU/mL at Week 4 were high and similar between assays used. At later time points, when viremia is low, assay concordance was high.