ArticleHepatology communications2017
The emergence of NS5B resistance associated substitution S282T after sofosbuvir-based treatment.
Article in Hepatology communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 2 of them syntheses that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Prevalence of Drug Resistance Associated Substitutions in Persons With Chronic Hepatitis C Infection and Virological Failure Following Initial or Re-treatment With Pan-genotypic Direct-Acting Antivirals: A Systematic Review and Meta-analysis.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2024Pooled it
- 2017 KASL clinical practice guidelines management of hepatitis C: Treatment of chronic hepatitis C.Clinical and molecular hepatology · 2018Guideline
- A Database-Derived Global Overview of HCV Resistance-Associated Substitutions: Characterizing Genotypic, Regional, and Temporal Heterogeneity.International journal of molecular sciences · 2026Article
- Identification of NS5B resistance-associated mutations in hepatitis C virus circulating in treatment-naïve Cameroonian patients.IJID regions · 2026Article
- Direct antiviral agents (DAAs) and their use in pregnant women with hepatitis C (HCV).Expert review of anti-infective therapy · 2022Review
- Emergence and Persistence of Resistance-Associated Substitutions in HCV GT3 Patients Failing Direct-Acting Antivirals.Frontiers in pharmacology · 2022Article
- Viral genome wide association study identifies novel hepatitis C virus polymorphisms associated with sofosbuvir treatment failure.Nature communications · 2021Article
- The Role of RASs /RVs in the Current Management of HCV.Viruses · 2021Review
- Akt Phosphorylation of Hepatitis C Virus NS5B Regulates Polymerase Activity and Hepatitis C Virus Infection.Frontiers in microbiology · 2021Article
- Distribution of naturally -occurring NS5B resistance-associated substitutions in Egyptian patients with chronic Hepatitis C.PloS one · 2021Article
- Inhibition of viral RNA-dependent RNA polymerases with clinically relevant nucleotide analogs.The Enzymes · 2021Article
- Priming of Antiviral CD8 T Cells without Effector Function by a Persistently Replicating Hepatitis C-Like Virus.Journal of virology · 2020Article
- Cell Culture Studies of the Efficacy and Barrier to Resistance of Sofosbuvir-Velpatasvir and Glecaprevir-Pibrentasvir against Hepatitis C Virus Genotypes 2a, 2b, and 2c.Antimicrobial agents and chemotherapy · 2020Article
- Prevalence of Naturally-Occurring NS5A and NS5B Resistance-Associated Substitutions in Iranian Patients With Chronic Hepatitis C Infection.Frontiers in microbiology · 2020Article
- Article
- Novel NS5B Resistance-Associated Substitution Emerges Under Failing Sofosbuvir/Ledipasvir Therapy.Clinical liver disease · 2019Review
- Status of Direct-Acting Antiviral Therapy for Hepatitis C Virus Infection and Remaining Challenges.Gastroenterology · 2019Review
- Review
Corrections and comments
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Authors and funding
17 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
S282T in NS5B is the primary amino acid substitution associated with resistance to sofosbuvir (SOF) but has rarely been detected in patients treated with a SOF-based regimen. Here, the emergence and fitness of the S282T substitution in virologic failure patients administered SOF-based regimens across the SOF and ledipasvir (LDV)/SOF phase 2 and 3 programs was evaluated. Plasma samples collected at baseline and at virologic failure were amplified and deep sequenced (1% cutoff). To date, over 12,000 patients have been treated in SOF or LDV/SOF phase 2 and 3 studies. Of these, deep sequencing was available at baseline in 8598 patients (62.4% genotype [GT] 1, 10.7% GT2, 20.9% GT3, and 6.0% GT4-6) and at virologic failure in 901 patients. In the 8598 patients, no S282T substitution was detected at baseline; at virologic failure, 10 of the 901 (1%) patients had S282T detected. The SOF-based regimen associated with treatment-emergent S282T was SOF monotherapy in two patients, retreatment with LDV/SOF in prior LDV/SOF failures in three patients, LDV/SOF for 8 weeks in 1 GT1 patient, LDV/SOF for 12 weeks in 1 patient each with GT3, GT4, and GT5, and LDV/SOF + ribavirin for 12 weeks in 1 GT6 patient. Nine of 10 patients with emergent S282T received an SOF-based retreatment regimen, eight of whom achieved sustained virologic response 12 weeks after treatment and one of whom failed retreatment.
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Registered trials
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