Baseline and Post-Treatment Hepatitis C NS5A Resistance in Relapsed Patients from a Multicentric Real-Life Cohort
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| Název: | Baseline and Post-Treatment Hepatitis C NS5A Resistance in Relapsed Patients from a Multicentric Real-Life Cohort |
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| Autoři: | Halfon, Philippe, Scholtes, Caroline, Izopet, Jacques, Larrat, Sylvie, Trimoulet, Pascale, Zoulim, Fabien, Alric, Laurent, Metivier, Sophie, Leroy, Vincent, Ouzan, Denis, Ledinghen, Victor De, Mohamed, Sofiane, Penaranda, Guillaume, Khiri, Hacène, Thélu, Marie-Ange, Plauzolles, Anne, Chiche, Laurent, Bourlière, Marc, Legrand-Abravanel, Florence |
| Přispěvatelé: | Pagès, Nathalie |
| Zdroj: | Antiviral Therapy. 23:307-314 |
| Informace o vydavateli: | SAGE Publications, 2017. |
| Rok vydání: | 2017 |
| Témata: | Male, 0301 basic medicine, Genotype, Viral Nonstructural Proteins / genetics, Antiviral Agents / therapeutic use, DNA Mutational Analysis, Drug Resistance, Hepacivirus, Viral Nonstructural Proteins, Antiviral Agents, Viral Nonstructural Proteins / antagonists & inhibitors, 03 medical and health sciences, Drug Therapy, Drug Resistance, Viral, Humans, Viral, Treatment Failure, 0303 health sciences, Viral Load, Hepatitis C, 3. Good health, [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, Treatment Outcome, Antiviral Agents / pharmacology, Hepatitis C / virology, Hepacivirus / drug effects, Drug Therapy, Combination, Female, Hepatitis C / drug therapy, Hepacivirus / genetics |
| Popis: | Background Recent data have suggested that failure to achieve sustained virological response with direct-acting antiviral therapy is usually due to relapse and is primarily associated with the emergence of resistance-associated substitutions. The aim of this study was to investigate the prevalence and characterization of non-structural-5A resistance-associated substitutions in patients infected with HCV genotypes 1, 3 and 4 treated by direct-acting antiviral therapy, including anti-non-structural-5A, and to characterize the pre-existing resistance-associated substitutions in subjects treated with anti-non-structural-5A inhibitors. Methods From January 2014 to March 2016, 2,995 patients infected with HCV genotypes 1, 3 and 4 were exposed to non-structural-5A inhibitors. Sequencing results at the time of virological failure were available for 61 patients; sequencing at baseline was available for 35 of these patients. Results Among the 35 patients with sequencing results available at baseline, 15 had no resistance-associated substitution, 16 had only one resistance-associated substitution, and 4 had more than one resistance-associated substitution. Resistance-associated substitutions were harbored in 57% of the sequences in the non-structural-5A region. Among the 61 patients sequenced at virological failure, 50 (82%) patients presented at least one resistance-associated substitutions inducing a high level of resistance to non-structural-5A inhibitors (>10-fold resistance). Conclusions This pooled analysis suggests that non-structural-5A resistance-associated substitutions screening should be recommended when considering retreatment with a non-structural-5A inhibitor regimen in patients who have previously experienced failed non-structural-5A treatment. |
| Druh dokumentu: | Article |
| Jazyk: | English |
| ISSN: | 2040-2058 1359-6535 |
| DOI: | 10.3851/imp3184 |
| Přístupová URL adresa: | https://pubmed.ncbi.nlm.nih.gov/28730994 https://www.ncbi.nlm.nih.gov/pubmed/28730994 https://pubmed.ncbi.nlm.nih.gov/28730994/ https://journals.sagepub.com/doi/abs/10.3851/IMP3184 https://www.intmedpress.com/journals/avt/abstract.cfm?id=3184&pid=48 |
| Rights: | URL: https://journals.sagepub.com/page/policies/text-and-data-mining-license |
| Přístupové číslo: | edsair.doi.dedup.....651d92d564ba9cda0bb0d52eb54f93d2 |
| Databáze: | OpenAIRE |
Nájsť tento článok vo Web of Science | Abstrakt: | Background Recent data have suggested that failure to achieve sustained virological response with direct-acting antiviral therapy is usually due to relapse and is primarily associated with the emergence of resistance-associated substitutions. The aim of this study was to investigate the prevalence and characterization of non-structural-5A resistance-associated substitutions in patients infected with HCV genotypes 1, 3 and 4 treated by direct-acting antiviral therapy, including anti-non-structural-5A, and to characterize the pre-existing resistance-associated substitutions in subjects treated with anti-non-structural-5A inhibitors. Methods From January 2014 to March 2016, 2,995 patients infected with HCV genotypes 1, 3 and 4 were exposed to non-structural-5A inhibitors. Sequencing results at the time of virological failure were available for 61 patients; sequencing at baseline was available for 35 of these patients. Results Among the 35 patients with sequencing results available at baseline, 15 had no resistance-associated substitution, 16 had only one resistance-associated substitution, and 4 had more than one resistance-associated substitution. Resistance-associated substitutions were harbored in 57% of the sequences in the non-structural-5A region. Among the 61 patients sequenced at virological failure, 50 (82%) patients presented at least one resistance-associated substitutions inducing a high level of resistance to non-structural-5A inhibitors (>10-fold resistance). Conclusions This pooled analysis suggests that non-structural-5A resistance-associated substitutions screening should be recommended when considering retreatment with a non-structural-5A inhibitor regimen in patients who have previously experienced failed non-structural-5A treatment. |
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| ISSN: | 20402058 13596535 |
| DOI: | 10.3851/imp3184 |