Resistance Mutations are Rare among Protease Inhibitor Treatment-Naive Hepatitis C Genotype-1 Patients with or without HIV Coinfection
| Autor: | João Renato Rebello Pinho, Fernanda de Mello Malta, Andrea G Leite, Flair José Carrilho, Flaviane Kesia Rodrigues, Michele Soares Gomes-Gouvêa, Leonora Z Piccoli, Caroline F Noble, Maria Cassia Mendes-Correa, Gaspar Lisboa-Neto, Mariliza Henrique da Silva, Mónica V Alvarado-Mora |
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| Rok vydání: | 2014 |
| Předmět: |
Adult
Male Genotype Hepacivirus Population HIV Infections Viral Nonstructural Proteins Antiviral Agents Drug Resistance Viral medicine Humans Protease Inhibitors Pharmacology (medical) Protease inhibitor (pharmacology) education Pharmacology education.field_of_study Polymorphism Genetic biology Coinfection virus diseases Hepatitis C Middle Aged Viral Load biology.organism_classification medicine.disease Virology Treatment Outcome Infectious Diseases Mutation Immunology Proofreading Female Viral load Brazil |
| Zdroj: | Antiviral Therapy. 20:281-287 |
| ISSN: | 2040-2058 1359-6535 |
| DOI: | 10.3851/imp2873 |
| Popis: | Background HCV has a high replication rate and a lack of proofreading activity, leading to a greatly diverse viral population. This diversity may lead to emergence of resistant strains in direct-acting antiviral therapy. The frequency of naturally occurring HCV protease inhibitor (PI) mutations has been addressed in many countries, but there are few data on the prevalence of these mutations in Brazilian patients. Methods We evaluated the sequence of HCV NS3 protease gene in 247 patients (135 HCV-monoinfected and 112 HIV–HCV-coinfected patients). HCV RNA was extracted from plasma and a fragment of 765 base pairs from the NS3 region was amplified and sequenced with Sanger-based technology. Results HIV–HCV-coinfected patients were more likely to be older than 40 years and have an HCV subtype-1a infection. Overall, 21.9% of patients had at least one amino acid substitution in the NS3 region; 14 patients (5.7%) harboured at least one resistance mutation (T54S, V55A, Q80R) and the Q80K mutation was not found in our case series. There was no difference between monoinfected and coinfected patients regarding the frequency of natural polymorphisms and resistance mutations. Conclusions Baseline HCV NS3 amino acid substitutions identified herein are considered mostly natural polymorphisms with no clinical impact on PI-based therapy. The identified resistance mutations may be associated with low-level resistance to PIs in vitro. Q80K substitution seems to be a rare event in Brazil. HIV coinfection was not associated with a greater frequency of such substitutions in the studied sample. |
| Databáze: | OpenAIRE |
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