ArticleAntimicrobial agents and chemotherapy2013
Persistence of resistant variants in hepatitis C virus-infected patients treated with the NS5A replication complex inhibitor daclatasvir.
Article in Antimicrobial agents and chemotherapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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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
40 citing papers in PubMed, 1 synthesis or guideline pooled it.
- SASLT guidelines: Update in treatment of Hepatitis C virus infection.Saudi journal of gastroenterology : official journal of the Saudi Gastroenterology Association · 2016Guideline
- Efficacy of daclatasvir/asunaprevir according to resistance-associated variants in chronic hepatitis C with genotype 1.Journal of gastroenterology · 2017Trial
- Preclinical and Clinical Resistance Profile of EDP-239, a Novel Hepatitis C Virus NS5A Inhibitor.Antimicrobial agents and chemotherapy · 2016Trial
- Naturally occurring dominant drug resistance mutations occur infrequently in the setting of recently acquired hepatitis C.Antiviral therapy · 2015Trial
- Real-world effectiveness of voxilaprevir/velpatasvir/sofosbuvir in patients following DAA failure.JHEP reports : innovation in hepatology · 2024Article
- Hepatitis C virus fitness can influence the extent of infection-mediated epigenetic modifications in the host cells.Frontiers in cellular and infection microbiology · 2023Article
- Efficacy of Glecaprevir/Pibrentasvir for Real-World HCV Infected Patients in the Northern Part of Tokyo, Japan.Journal of clinical medicine · 2021Article
- Review
- Article
- Real-word efficacy of sofosbuvir, velpatasvir plus ribavirin therapy for chronic hepatitis patients who failed to prior DAA therapy with NS5A-P32 deletion mutated HCV infection.Clinical journal of gastroenterology · 2020Article
- Single-molecular real-time deep sequencing reveals the dynamics of multi-drug resistant haplotypes and structural variations in the hepatitis C virus genome.Scientific reports · 2020Article
- Prevalence of Naturally-Occurring NS5A and NS5B Resistance-Associated Substitutions in Iranian Patients With Chronic Hepatitis C Infection.Frontiers in microbiology · 2020Article
- NS5A-P32 deletion as a factor involved in virologic failure in patients receiving glecaprevir and pibrentasvir.Journal of gastroenterology · 2019Article
- Combinations of two drugs among NS3/4A inhibitors, NS5B inhibitors and non-selective antiviral agents are effective for hepatitis C virus with NS5A-P32 deletion in humanized-liver mice.Journal of gastroenterology · 2019Article
- Impact of novel NS5A resistance-associated substitutions of hepatitis C virus detected in treatment-experienced patients.Scientific reports · 2019Article
- Challenge to overcome: Nonstructural protein 5A-P32 deletion in direct-acting antiviral-based therapy for hepatitis C virus.World journal of gastroenterology · 2018Article
- Integrated pharmacokinetic/viral dynamic model for daclatasvir/asunaprevir in treatment of patients with genotype 1 chronic hepatitis C.Acta pharmacologica Sinica · 2018Article
- Characterization of hepatitis C virus resistance to grazoprevir reveals complex patterns of mutations following on-treatment breakthrough that are not observed at relapse.Infection and drug resistance · 2018Article
- Prevalence of naturally occurring NS5A resistance-associated substitutions in patients infected with hepatitis C virus subtype 1a, 1b, and 3a, co-infected or not with HIV in Brazil.BMC infectious diseases · 2017Article
- Low frequency of NS5A relevant resistance-associated substitutions to Elbasvir among hepatitis C virus genotype 1a in Spain: a cross-sectional study.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Daclatasvir (DCV; BMS-790052) is a hepatitis C virus (HCV) NS5A replication complex inhibitor (RCI) with picomolar to low nanomolar potency and broad genotypic coverage in vitro. Viral RNA declines have been observed in the clinic for both alpha interferon-ribavirin (IFN-α-RBV) and IFN-RBV-free regimens that include DCV. Follow-up specimens (up to 6 months) from selected subjects treated with DCV in 14-day monotherapy studies were analyzed for genotype and phenotype. Variants were detected by clonal sequencing in specimens from baseline and were readily detected by population sequencing following viral RNA breakthrough and posttreatment. The major amino acid substitutions generating resistance in vivo were at residues M28, Q30, L31, and Y93 for genotype 1a (GT-1a) and L31 and Y93 for GT-1b, similar to the resistance substitutions observed with the in vitro replicon system. The primary difference in the resistance patterns observed in vitro and in vivo was the increased complexity of linked variant combinations observed in clinical specimens. Changes in the percentage of individual variants were observed during follow-up; however, the overall percentage of variants in the total population persisted up to 6 months. Our results suggest that during the 14-day monotherapy, most wild-type virus was eradicated by DCV. After the end of DCV treatment, viral fitness, rather than DCV resistance, probably determines which viral variants emerge as dominant in populations.
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