BACKGROUND: Response-guided therapy (RGT) for HCV treatment, whereby therapy duration is shortened according to on-treatment virological response, requires patient HCV RNA concentrations below the lower limit of quantification (LLOQ) or limit of detection (LOD) of the viral load assay at weeks 4 and 12. Concordance of two assays and impact on treatment decisions were investigated. METHODS: Plasma samples (n=1,411; baseline to week 12) from HCV genotype-1-infected patients (n=290) receiving simeprevir (TMC435) plus pegylated interferon-α2a/ribavirin in the PILLAR study (NCT00882908) were analysed using Roche High-Pure-System/COBAS(®) TaqMan(®) v2.0 assay (HPS; LLOQ 25 IU/ml and LOD 15 IU/ml; Roche Diagnostics, Indianapolis, IN, USA) and reanalysed using Abbott realtime assay (ART; LLOQ and LOD 12 IU/ml; Abbott Molecular Inc., Des Plaines, IL, USA). RESULTS: Overall, 217/766 (28.3%) samples from different time points with HCV RNA undetectable by HPS had HCV RNA detectable by ART. Conversely, 35/584 (6.0%) samples undetectable by ART were detectable by HPS. For both assays, most discrepant samples (96-100%) had HCV RNA<25 IU/ml. At week 4, 75.5% of samples were undetectable by HPS, whereas 49.4% were undetectable by ART, resulting in different RGT assessment in 26.1% (P<0.0001). At week 12, 95.4% and 91.9% of samples were undetectable with HPS and ART, respectively. CONCLUSIONS: Lower rates of undetectable HCV RNA with ART at week 4 suggest that if RGT criteria are determined with ART, the proportion of patients qualifying for shorter treatment duration may be significantly lower (26%). Therefore, different RGT criteria may be necessary for ART to maximize numbers benefiting from shortened treatment. Further testing and validation are required.
BACKGROUND: Response-guided therapy (RGT) for HCV treatment, whereby therapy duration is shortened according to on-treatment virological response, requires patient HCV RNA concentrations below the lower limit of quantification (LLOQ) or limit of detection (LOD) of the viral load assay at weeks 4 and 12. Concordance of two assays and impact on treatment decisions were investigated. METHODS: Plasma samples (n=1,411; baseline to week 12) from HCV genotype-1-infectedpatients (n=290) receiving simeprevir (TMC435) plus pegylated interferon-α2a/ribavirin in the PILLAR study (NCT00882908) were analysed using Roche High-Pure-System/COBAS(®) TaqMan(®) v2.0 assay (HPS; LLOQ 25 IU/ml and LOD 15 IU/ml; Roche Diagnostics, Indianapolis, IN, USA) and reanalysed using Abbott realtime assay (ART; LLOQ and LOD 12 IU/ml; Abbott Molecular Inc., Des Plaines, IL, USA). RESULTS: Overall, 217/766 (28.3%) samples from different time points with HCV RNA undetectable by HPS had HCV RNA detectable by ART. Conversely, 35/584 (6.0%) samples undetectable by ART were detectable by HPS. For both assays, most discrepant samples (96-100%) had HCV RNA<25 IU/ml. At week 4, 75.5% of samples were undetectable by HPS, whereas 49.4% were undetectable by ART, resulting in different RGT assessment in 26.1% (P<0.0001). At week 12, 95.4% and 91.9% of samples were undetectable with HPS and ART, respectively. CONCLUSIONS: Lower rates of undetectable HCV RNA with ART at week 4 suggest that if RGT criteria are determined with ART, the proportion of patients qualifying for shorter treatment duration may be significantly lower (26%). Therefore, different RGT criteria may be necessary for ART to maximize numbers benefiting from shortened treatment. Further testing and validation are required.
Authors: F Wiesmann; G Naeth; C Sarrazin; A Berger; R Kaiser; R Ehret; H Knechten; P Braun Journal: Med Microbiol Immunol Date: 2014-11-15 Impact factor: 3.402
Authors: R K Sterling; A Kuo; V K Rustgi; M S Sulkowski; T G Stewart; J M Fenkel; H El-Genaidi; M A Mah'moud; G M Abraham; P W Stewart; L Akushevich; D R Nelson; M W Fried; A M Di Bisceglie Journal: Aliment Pharmacol Ther Date: 2015-01-28 Impact factor: 8.171
Authors: Robert Strassl; Karoline Rutter; Albert Friedrich Stättermayer; Sandra Beinhardt; Michael Kammer; Harald Hofer; Peter Ferenci; Theresia Popow-Kraupp Journal: PLoS One Date: 2015-08-14 Impact factor: 3.240
Authors: Benjamin Maasoumy; Bela Hunyady; Vincenza Calvaruso; Mihály Makara; Johannes Vermehren; Attila Haragh; Simone Susser; Birgit Bremer; Gavin Cloherty; Michael P Manns; Antonio Craxì; Heiner Wedemeyer; Christoph Sarrazin Journal: PLoS One Date: 2014-11-12 Impact factor: 3.240
Authors: F Wiesmann; G Naeth; A Berger; H H Hirsch; S Regenass; R S Ross; C Sarrazin; H Wedemeyer; H Knechten; P Braun Journal: Med Microbiol Immunol Date: 2015-12-14 Impact factor: 3.402