1425 Simeprevir (Tmc435) With Peginterferon/Ribavirin for Chronic HCV Genotype-1 Infection in Treatment-Naïve Patients: Results From Quest-1, a Phase Iii Trial

Jacobson, Ira M.; Dore, G.J.; Foster, Graham; Fried, Michael; Radu, Marius; Rafalskiy, Vladimir V.; Мороз, Л. В.; Craxı̀, Antonio; Peeters, Monika; Lenz, Oliver; Ouwerkerk‐Mahadevan, Sivi; Kalmeijer, Ronald; Beumont–Mauviel, Maria

doi:10.1016/s0168-8278(13)61424-5

Cited by 98 publications

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“…Simeprevir plus peg-IFN/RBV treatment achieves rates of SVR similar to those for peg-IFN/RBV treatment in HCV-1a-infected patients who present the viral variation Q80K. This variation is frequent in the HCV-1a subtype, but it is not found in HCV-1b (2,5). Similarly, daclatasvir plus peg-IFN/RBV treatment also achieves higher SVR rates among HCV1b-infected patients than among HCV-1a-infected individuals (4).…”

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confidence: 70%

“…This is the case for simeprevir, a DAA recently approved for clinical use, that in combination with pegylated interferon and ribavirin (peg-IFN/ RBV) has a lower sustained virological response (SVR) rate for subtype 1a than for 1b (2). Simeprevir plus peg-IFN/RBV treatment achieves rates of SVR similar to those for peg-IFN/RBV treatment in HCV-1a-infected patients who present the viral variation Q80K.…”

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confidence: 99%

“…he effect of the hepatitis C virus (HCV) genotype 1 subtype on the response to treatment can be dramatic for some direct antiviral agent (DAA)-containing regimens (1)(2)(3)(4)(5)(6)(7)(8)(9). This is the case for simeprevir, a DAA recently approved for clinical use, that in combination with pegylated interferon and ribavirin (peg-IFN/ RBV) has a lower sustained virological response (SVR) rate for subtype 1a than for 1b (2).…”

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Reassessment of Genotype 1 Hepatitis C Virus Subtype Misclassification by LiPA 2.0: Implications for Direct-Acting Antiviral Treatment

et al. 2014

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The accuracy of LiPA 2.0 for hepatitis C virus 1 (HCV-1) subtype classification was analyzed. LiPA 2.0 genotype results from 101 HCV-1-infected patients were compared to genotype findings determined by direct core sequencing. Eleven (11%) samples were misclassified. Given the influence of the HCV-1-subtype in the anti-HCV therapy response, an alternative classification method is warranted.T he effect of the hepatitis C virus (HCV) genotype 1 subtype on the response to treatment can be dramatic for some direct antiviral agent (DAA)-containing regimens (1)(2)(3)(4)(5)(6)(7)(8)(9). This is the case for simeprevir, a DAA recently approved for clinical use, that in combination with pegylated interferon and ribavirin (peg-IFN/ RBV) has a lower sustained virological response (SVR) rate for subtype 1a than for 1b (2). Simeprevir plus peg-IFN/RBV treatment achieves rates of SVR similar to those for peg-IFN/RBV treatment in HCV-1a-infected patients who present the viral variation Q80K. This variation is frequent in the HCV-1a subtype, but it is not found in HCV-1b (2, 5). Similarly, daclatasvir plus peg-IFN/RBV treatment also achieves higher SVR rates among HCV1b-infected patients than among HCV-1a-infected individuals (4). For interferon-free regimens, DAA combinations such as asunaprevir plus daclatasvir may only be indicated for subtype 1b, because of high relapse rates observed among patients with subtype 1a (3, 4). Because of these, accurate subtyping of HCV genotype 1-infected patients is needed for those who are candidates for DAAs.Sequencing of specific HCV genome regions with subsequent phylogenetic analysis is considered the gold standard of HCV genotyping (10). However, it includes several complex techniques and is time consuming. For these reasons, LiPA 2.0 is currently one of the most widely used genotyping assays. However, several studies have reported HCV genotyping errors using this commercial method (11-13). Those studies were not designed to evaluate the frequency of HCV-1 subtyping misclassifications, and they included few HCV-1-infected patients. Therefore, due to the high prevalence of HCV-1 infections in western countries and the importance of correct subtyping in clinical decisions, the accuracy of this method for HCV-1 subtyping needs to be evaluated in larger samples. For these reasons, we aimed to evaluate the accuracy of LiPA 2.0 for classifying HCV-1 by subtypes.This study was performed according to the ethical guidelines of the 1975 Declaration of Helsinki, and it was approved by the ethics committee of the Hospital Universitario de Valme (Seville, Spain).The first 110 consecutive patients starting from October 2001, who received a course of peg-IFN/RBV treatment in our hospital and who were infected with HCV-1, according to the LiPA 2.0 determination, were selected. All of them were Caucasian with a median age (quartile 1 to quartile 3) of 42 years (range, 39 to 46 years). Among the patients, 82 (81%) were male, and 48 (47.5%) were infected with HIV.To determine the HCV-1 subtype, we analyzed...

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Reassessment of Genotype 1 Hepatitis C Virus Subtype Misclassification by LiPA 2.0: Implications for Direct-Acting Antiviral Treatment

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“…Combination therapy with simeprevir was also evaluated in the treatment of previous null and partial responders. The addition of simeprevir (12-48 weeks) + PEG-IFN + RBV (48 weeks) in previous null and partial responders and relapsers showed high rates of SVR (67-80%) compared with PEG-IFN + RBV [Jacobson et al 2013a]. However, similar to what was observed with BOC-and TPV-based combination therapies, SVR rates were lower in subgroups of null responders (41-59%) and partial responders (65-86%) than previous relapsers (76-89%).…”

Section: Combination Therapy With Peg-ifn Rbv and A Second-generatiomentioning

confidence: 97%

Beyond interferon: rationale and prospects for newer treatment paradigms for chronic hepatitis C

Cortez

Kottilil

2014

Therapeutic Advances in Chronic Disease

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Hepatitis C virus (HCV) infection results in a chronic carrier state in 80% of individuals infected with the virus and presently affects over 170 million people worldwide. Approximately 20% of those chronically infected will ultimately progress to develop cirrhosis and death due to end-stage liver disease or hepatocellular carcinoma (HCC). Unlike many other chronic viral infections, effective treatments for HCV are available. Cure from the infection is known as a sustained virologic response (SVR). SVR is associated with reversal of the long-term outcomes of chronic liver disease, decrease in incidence of HCC, and decrease HCV attributable mortality. The current FDA approved therapies for hepatitis C virus genotype 1 (GT-1) include pegylated interferon (PEG-IFN) and ribavirin (RBV) in combination with a directly acting antiviral agent (DAA). New therapeutic advances are being made aiming to simplify management, improve the tolerability of treatment, and shorten the duration of therapy. Moreover, treatment regimens that will effectively eradicate hepatitis C without the use of interferon formulations (IFN) are being developed. In this review, we report the transition of HCV therapeutics from an interferon-α based combination therapy to an all-oral, directly acting antiviral therapy.

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“…Second-wave PIs have a higher barrier to resistance, better activity against multiple genotypes except GT-3, more convenient dosing schedules and improved safety and tolerance [Ciesek et al 2011;Fusco et al 2011;Asselah et al 2011]. Second-generation PIs are compounds that are broadly active against all genotypes and against viral isolates that carry resistance mutations for first-generation PIs [Jacobson et al 2013;Manns et al 2013a;Zeuzem et al 2012a;Ferenci et al 2013;Sulkowski et al 2013aSulkowski et al , 2013bEverson et al 2012a;Feld et al 2012;Manns et al 2012;Lawitz et al 2011bLawitz et al , 2012bPoordad et al 2012a;Bronowicki et al 2012;Lok et al 2012b]. In combination with PR, the new PIs appear to achieve greater SVR rates than the first-generation PIs.…”

Section: Treatment Of Gt-1 Patients Beyond Boceprevir or Telaprevirmentioning

confidence: 99%

An update on the treatment of genotype-1 chronic hepatitis C infection: lessons from recent clinical trials

Wendt

Bourlière

2013

Therapeutic Advances in Infection

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The launch of first-generation protease inhibitors (PIs) was a major step forward in hepatitis C virus (HCV) treatment. However, this major advance is, up to now, restricted to genotype-1 (GT-1) patients. However, the ongoing development of new direct-acting antiviral agents (DAAs) allows new hope for the future. The development of second-wave and second-generation PIs yields higher antiviral potency through plurigenotypic activity, more convenient daily administration, fewer side effects and, for the second-generation PIs, potential activity against resistance-associated variants. NS5B inhibitors (NS5B.I) include nucleoside/nucleotide inhibitors (NIs) and nonnucleotide inhibitors (NNIs). NIs have high efficacy across all genotypes. Sofosbuvir has highly potent antiviral activity across all genotypes in association with pegylated interferon (IFN) and ribavirin (PR), thus allowing shortened treatment duration. NS5A inhibitors (NS5A.I) have highly potent antiviral activity. It has recently been shown for the first time that NS5A.I in combination with PI can cure GT-1b null-responder patients in an IFN-free regimen. In addition, several studies demonstrate that IFN-free regimens with DAA combinations are able to cure a large number of either naïve or treatment-experienced GT-1 patients. Moreover, a quadruple regimen with PR is able to cure almost all GT-1 null-responders. The development of pan-genotypic DAAs (NIs or NS5A.I) allows new combinations with or without PR that increase the rate of sustained virological response (SVR) for all patients, even for those with cirrhosis and independently of the genotype. Therefore, the near future of HCV treatment looks promising. The purpose of this article is to provide an overview of the clinical results recently reported for HCV treatment in GT-1 patients.

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1425 Simeprevir (Tmc435) With Peginterferon/Ribavirin for Chronic HCV Genotype-1 Infection in Treatment-Naïve Patients: Results From Quest-1, a Phase Iii Trial

Cited by 98 publications

References 0 publications

Reassessment of Genotype 1 Hepatitis C Virus Subtype Misclassification by LiPA 2.0: Implications for Direct-Acting Antiviral Treatment

Reassessment of Genotype 1 Hepatitis C Virus Subtype Misclassification by LiPA 2.0: Implications for Direct-Acting Antiviral Treatment

Beyond interferon: rationale and prospects for newer treatment paradigms for chronic hepatitis C

An update on the treatment of genotype-1 chronic hepatitis C infection: lessons from recent clinical trials

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