Resistance Analyses for Ledipasvir/Sofosbuvir Containing Regimens in Patients Infected with Chronic HCV who Have Advanced Liver Disease or are Post Liver Transplant (Solar-1 &amp; 2 Studies)

Charlton, Michael; Manns, M.; Dvory‐Sobol, Hadas; Svarovskaia, Evguenia; Doehle, Brian P.; Arterburn, Sarah; Cao, Yun; Brainard, Diana M.; McHutchison, John G.; Miller, Michael D.; Mo, Hongmei; Afdhal, Nezam H.; Dj, Mutimer

doi:10.1016/s0168-8278(16)01701-3

Cited by 4 publications

(4 citation statements)

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“…Moreover, an analysis of more than 7800 NS5A and NS5B sequences from HCV-infected patients across 22 countries showed a prevalence of up to 34% for the L159F mutation in GT1b infected patients [ 33 ]. Several studies analyzing the natural presence of NS5B RASs equally refute an associated significant impact on SVR12 rates [ 49 , 50 ], which further strengthens this study’s data.…”

Section: Discussionsupporting

confidence: 85%

“…Along these lines, baseline NS5 RASs seem to have minimal effects on patient responses to sofosbuvir plus NS5A inhibitors (LDV, DCV, VEL) based therapies. It is well established through cumulative research data that, when baseline NS5A RASs in particular do have effects, they could be largely overcome by extending treatment duration and/or through treatment intensification with the addition of RBV, which drastically reduced the impact of NS5A baseline RASs [ 25 , 49 , 54 , 55 , 56 ]. Additionally, the cost-effectiveness of baseline resistance testing was accessed in a recent paper describing how the inquiry of baseline NS5A RASs prior to treatment with EBR/GZR is a cost-effective measure resulting in more QALYs (quality-adjusted life years) among GT1a treatment-naive or treatment-experienced patients when compared to a treatment with EBR/GZR without baseline resistance testing.…”

Section: Discussionmentioning

confidence: 99%

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Characterization of NS5A and NS5B Resistance-Associated Substitutions from Genotype 1 Hepatitis C Virus Infected Patients in a Portuguese Cohort

Brandão

Marcelino

Gonçalves

et al. 2018

Viruses

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This study is focused on the prevalent NS5 coding region resistance-associated substitutions (RASs) in DAA-naive genotype (GT)1 HCV-infected patients and their potential impact on success rates. Plasma RNA from 81 GT1 HCV-infected patients was extracted prior to an in-house nested RT-PCR of the NS5 coding region, which is followed by Sanger population sequencing. NS5A RASs were present in 28.4% (23/81) of all GT1-infected patients with 9.9% (8/81) having the Y93C/H mutation. NS5B RASs showed a prevalence of 14.8% (12/81) and were only detected in GT1b. Overall 38.3% (31/81) of all GT1 HCV-infected patients presented baseline RASs. The obtained data supports the usefulness of resistance testing prior to treatment since a statistically significant association was found between treatment failure and the baseline presence of specific NS5 RASs known as Y93C/H (p = 0.04).

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Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Characterization of NS5A and NS5B Resistance-Associated Substitutions from Genotype 1 Hepatitis C Virus Infected Patients in a Portuguese Cohort

Brandão

Marcelino

Gonçalves

et al. 2018

Viruses

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“…In contrary to this result, in a UNITY-1 study, despite the higher frequency of NS5A RASs was observed prior to treatment in GT1b compared to GT1a infected patients (16% vs 11%), all subjects with GT1b infection achieved SVR in contrast to only 74% for GT1a [95,96].Nevertheless, a recent study showed an exciting result that the impact of baseline NS5A RASs on outcome of treatment can be significantly reduced or even completely removed when patients go through a longer duration of treatment with SOF + LDV and addition of RBV [96]. Furthermore, pre-existing RASs in NS5A appeared to have little effect on the outcome of treatment regimen with SOF + VEL, in spite of a high frequency of such variants, 97-100% subjects with baseline resistance in NS5A achieved SVR [97,98].…”

Section: Drug Resistancementioning

confidence: 99%

Direct-acting Antiviral in the Treatment of Chronic Hepatitis C: Bonuses and Challenges

Zeng¹,

Li²,

Hou³

et al. 2020

Int. J. Med. Sci.

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Owing to the rapid development and wide clinical application of direct acting antiviral (DAA) drugs in the treatment of hepatitis C virus (HCV) infection, the era of interferon-based therapy has almost come to an end. Cumulative studies show that DAA therapy renders high cure efficiency (>90%) and good safety profile, and may even bring some unexpected benefits to the patients. However, some issues of concern arise, one of which is the resistance mutation of HCV genome leading to failure of treatment. With the aim of providing some meaningful references for the treatment of chronic hepatitis C (CHC), this article summarizes the research progress on benefits of DAA accompanied by viral clearance in the treatment of chronic hepatitis and the drug resistance.

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“…Only 50% of the patients that had two or more baseline resistance‐related variants cleared the virus, with the lowest SVR rates observed with variant Y93H/N . A recent study showed that a longer duration of treatment with SOF + LDV and addition of RBV can reduce or even eliminate the impact of baseline NS5A RAVs .…”

Section: Introductionmentioning

confidence: 99%

Impact of HCV genotype on treatment regimens and drug resistance: a snapshot in time

Cuypers

Ceccherini‐Silberstein

Laethem

et al. 2016

Reviews in Medical Virology

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The introduction of highly potent direct-acting antivirals (DAAs) has revolutionized hepatitis C virus treatment. Nevertheless, viral eradication worldwide remains a challenge also in the era of DAA treatment, because of the high associated costs, high numbers of undiagnosed patients, high re-infection rates in some risk groups and suboptimal drug efficacies associated with host and viral factors as well as advanced stages of liver disease. A correct determination of the HCV genotype allows administration of the most appropriate antiviral regimen. Additionally, HCV genetic sequencing improves our understanding of resistance-associated variants, either naturally occurring before treatment, acquired by transmission at HCV infection, or emerging after virological failure. Because treatment response rates, and the prevalence and development of drug resistance variants differ for each DAA regimen and HCV genotype, this review summarizes treatment opportunities per HCV genotype, and focuses on viral genetic sequencing to guide clinical decision making. Although approval of the first pan-genotypic DAA-only regimen is expected soon, HCV genetic sequencing will remain important because when DAA therapies fail, genotyping and resistance testing to select a new active DAA combination will be essential. Copyright © 2016 John Wiley & Sons, Ltd.

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Resistance Analyses for Ledipasvir/Sofosbuvir Containing Regimens in Patients Infected with Chronic HCV who Have Advanced Liver Disease or are Post Liver Transplant (Solar-1 & 2 Studies)

Cited by 4 publications

References 0 publications

Characterization of NS5A and NS5B Resistance-Associated Substitutions from Genotype 1 Hepatitis C Virus Infected Patients in a Portuguese Cohort

Characterization of NS5A and NS5B Resistance-Associated Substitutions from Genotype 1 Hepatitis C Virus Infected Patients in a Portuguese Cohort

Direct-acting Antiviral in the Treatment of Chronic Hepatitis C: Bonuses and Challenges

Impact of HCV genotype on treatment regimens and drug resistance: a snapshot in time

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