HCV RNA Quantification with Different Assays: Implications for Protease-Inhibitor-Based Response-Guided Therapy

Fevery, Bart; Susser, S.; Lenz, Oliver; Cloherty, Gavin; Perner, D.; Picchio, Gastón; Sarrazin, Christoph

doi:10.3851/imp2760

Cited by 32 publications

(24 citation statements)

References 19 publications

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“…Although our study did not include repeated measurements of samples to address assay variability and the treatment duration decision was predefined based on the HPS assay used in the OPTIMIZE study, the data presented here are in line with the results of the comparison of the HPS and ART assays on samples from patients treated with other DAAs combined with Peg-IFN/ RBV therapy (16,17). These studies also suggested that 12 IU/ml is a more appropriate cutoff for response-guided treatment for a DAA-based triple therapy when the ART assay is used for HCV RNA quantification.…”

Section: Discussionsupporting

confidence: 66%

“…Discordant results between the assays were mostly observed in samples with values bordering the LOQ and LOD. As previously reported, the ART assay demonstrated higher sensitivity for detection of the HCV load in the low range than the HPS assay (16,17,23). Overall, for 15% of patients who had no viral RNA detected by HPS, RNA was still detectable by ART.…”

Section: Discussionsupporting

confidence: 52%

“…A lower rate of undetectable HCV RNA at early time points was observed with ART than with HPS (16)(17)(18).…”

mentioning

confidence: 99%

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An OPTIMIZE Study Retrospective Analysis for Management of Telaprevir-Treated Hepatitis C Virus (HCV)-Infected Patients by Use of the Abbott RealTi m e HCV RNA Assay

et al. 2015

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e Protease inhibitor (PI)-based response-guided triple therapies for hepatitis C virus (HCV) infection are still widely used. Noncirrhotic treatment-naive and prior relapser patients receiving telaprevir-based treatment are eligible for shorter, 24-week total therapy if HCV RNA is undetectable at both weeks 4 and 12. In this study, the concordance in HCV RNA assessments between the Roche High Pure System/Cobas TaqMan and Abbott RealTime HCV RNA assays and the impacts of different HCV RNA cutoffs on treatment outcome were evaluated. A total of 2,629 samples from 663 HCV genotype 1 patients receiving telaprevir/pegylated interferon/ribavirin in OPTIMIZE were analyzed using the High Pure System and reanalyzed using Abbott RealTime (limits of detection, 15.1 IU/ml versus 8.3 IU/ml; limits of quantification, 25 IU/ml versus 12 IU/ml, respectively). Overall, good concordance was observed between the assays. Using undetectable HCV RNA at week 4, 34% of the patients would be eligible for shorter treatment duration with Abbott RealTime versus 72% with the High Pure System. However, using <12 IU/ml for Abbott RealTime, a similar proportion (74%) would be eligible. Of the patients receiving 24-week total therapy, 87% achieved a sustained virologic response with undetectable HCV RNA by the High Pure System or <12 IU/ml by Abbott RealTime; however, 92% of the patients with undetectable HCV RNA by Abbott RealTime achieved a sustained virologic response. Using undetectable HCV RNA as the cutoff, the more sensitive Abbott RealTime assay would identify fewer patients eligible for shorter treatment than the High Pure System. Our data confirm the <12-IU/ml cutoff, as previously established in other studies of the Abbott RealTime assay, to determine eligibility for shortened PI-based HCV treatment. (The study was registered with ClinicalTrials.gov under registration no. NCT01241760.)

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Section: Discussionsupporting

confidence: 66%

Section: Discussionsupporting

confidence: 52%

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An OPTIMIZE Study Retrospective Analysis for Management of Telaprevir-Treated Hepatitis C Virus (HCV)-Infected Patients by Use of the Abbott RealTi m e HCV RNA Assay

et al. 2015

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“…Interestingly, the assay is more sensitive around the lower limit of quantification (LLOQ) when compared to the CAP/CTM and HPS/CTM assays. This has led to the observation that many on-treatment or even post-treatment specimens that had results reported as ''target not detected" by HPS/CTM or CAP/CTM showed detectable/not quantifiable or even quantifiable results by the ART assay [22,[39][40][41][42].…”

Section: Real-time Pcr Technologymentioning

confidence: 96%

“…Thus, eligibility for shortened therapy should be based on attainment of undetectable HCV RNA at week 4 only, whereas patients with detectable/not quantifiable (<25 IU/ml) HCV RNA should receive a full course of therapy [43]. However, the HPS/CTM assay that was used in these trials has been shown to be less sensitive compared to CAP/CTM and ART, which are mostly used in clinical routine [39,44,57]. Indeed, some data suggest that assay-specific RGT criteria may be required given the significant performance differences among HCV RNA assays.…”

Section: The Role Of Hcv Rna Quantification During Protease Inhibitormentioning

confidence: 98%

Diagnostics in hepatitis C: The end of response-guided therapy?

Maasoumy

Vermehren

2016

Journal of Hepatology

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On-treatment hepatitis C virus (HCV) RNA has been used to predict response to interferon (IFN)-based therapy. The concept of response-guided treatment (RGT) was established to determine optimal treatment duration and to early identify patients not responding to futile therapies. RGT helped to improve sustained virologic response (SVR) rates and lower the rates of adverse effects. RGT was of particular importance for telaprevir- and boceprevir-based triple therapies. RGT strategies are dependent on highly sensitive and reproducible HCV RNA quantification. However, different HCV RNA assays are used in routine clinical practice and these differ significantly in their performance characteristics. The development of IFN-free therapies has fundamentally changed the role of on-treatment HCV RNA for SVR prediction. Given the high efficacy and excellent tolerability of IFN-free regimens, the interest in treatment individualization has decreased. However, shorter treatment durations may still be desirable, particularly with respect to the high costs of current IFN-free direct-acting antiviral agents (DAAs). Moreover, some difficult-to-treat patients remain, e.g., those infected with HCV genotype 3 in whom the current standard of care may not always be sufficient to achieve SVR, especially in treatment-experienced patients with cirrhosis. Here, a RGT extension may be feasible. However, current data on the predictive value of on-treatment HCV RNA are limited and have shown conflicting results. As more potent DAAs become available, the role of response prediction may diminish further. Currently, shorter treatment duration is only based on baseline HCV RNA whereas no RGT strategy is recommended for any of the approved DAA regimens available.

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Significance of detectable HCV RNA below the limit of quantification in patients treated with DAAs using standard and ultrasensitive protocols

Comandini

Lapa

Lionetti

et al. 2018

Journal of Medical Virology

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Predictive factors of HCV relapse after treatment with DAAs are poorly understood. In this study, we aimed to assess whether the residual viral load positivity observed during or at the end of treatment (EOT) has an impact on viral outcome. Blood samples were collected from 337 patients with genotypes (GT) 1a, 1b, 2, 3, and 4 HCV chronic infection, treated with DAAs to determine HCV RNA load by the Abbott RealTime HCV (ART) assay at treatment week (W) 4, at EOT, and 4, 12, 24 weeks after discontinuation. EOT and other samples with "detected <12/mL" (DNQ) were retested by an ultrasensitive protocol (USP) to confirm the result. Frequency of DNQ was analyzed in subgroups of patients and clinical conditions to assess potential correlations. At W4, 22% and 30.9% of the samples were undetectable and DNQ by ART assay, respectively, but no correlation for achieving SVR was found. In contrast, an HCV RNA cut-off of ≥50/mL at W4 was a significant predictor of therapy failure (P = 0.036, univariate analysis). At EOT, DNQ was associated to 12W treatment duration (P < 0.001) and GT1a infection (P = 0.036). Overall, 20/41 (48.8%) of DNQ samples at EOT or post-treatment W4, were confirmed by USP but only in a single case the patient experienced viral relapse. HCV RNA at W4 can predict SVR, irrespective to genotype or DAA regimen. HCV RNA DNQ at EOT is associated to shorter treatment duration and to GT1a, but is not a predictor of therapy failure.

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HCV RNA Quantification with Different Assays: Implications for Protease-Inhibitor-Based Response-Guided Therapy

Cited by 32 publications

References 19 publications

An OPTIMIZE Study Retrospective Analysis for Management of Telaprevir-Treated Hepatitis C Virus (HCV)-Infected Patients by Use of the Abbott RealTi m e HCV RNA Assay

An OPTIMIZE Study Retrospective Analysis for Management of Telaprevir-Treated Hepatitis C Virus (HCV)-Infected Patients by Use of the Abbott RealTi m e HCV RNA Assay

Diagnostics in hepatitis C: The end of response-guided therapy?

Significance of detectable HCV RNA below the limit of quantification in patients treated with DAAs using standard and ultrasensitive protocols

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