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Net emergence of substitutions at position 28 in NS5A of hepatitis C virus genotype 4 in patients failing direct-acting antivirals detected by next-generation sequencing
- Source :
- International Journal of Antimicrobial Agents, International Journal of Antimicrobial Agents, 2019, 53, pp.80-83. ⟨10.1016/j.ijantimicag.2018.09.010⟩
- Publication Year :
- 2019
- Publisher :
- Elsevier BV, 2019.
-
Abstract
- More data on resistance of HCV genotype (GT) 3 and 4 to direct-acting antivirals (DAAs) are still needed. Here we investigated the presence of resistance-associated substitutions (RASs) pre- and post-treatment and their emergence under DAAs in HCV GT3- and GT4-infected patients failing DAA regimens by next-generation sequencing (NGS). Sanger sequencing and NGS were performed on NS5B and NS5A in plasma samples prior to and post treatment of 13 patients. Positions implicated in resistance to anti-NS5A and anti-NS5B in the literature were analysed. No baseline RASs was detected in NS5B but one GT4r virus developed the mutation S282T at failure. In NS5A, pre-existing RASs or polymorphisms were detected in viruses of 6/10 patients (L28M for a GT4a, M28V for a GT4r, L30R for a GT4a, 2 GT4d and 1 GT4r, and T58P for a GT4d) by Sanger sequencing and in viruses of 7/10 patients by NGS. Additional baseline minority substitutions detected by NGS were Y93H in a GT3a, L28M in a GT4a and GT4d, and L28F in a GT4d virus. At failure, these substitutions were found at a frequency of 100%. Y93H was detected alone at baseline, whilst L28M and L28F were accompanied by polymorphisms L30R or L30R + T58P. Use of NGS in patients failing DAAs and infected by HCV GT3 and GT4 revealed the emergence of specific patterns of substitutions in NS5A and NS5B, in particular substitutions at position 28 in NS5A in GT4 virus, highlighting the need to list these substitutions in guidelines for resistance interpretation.
- Subjects :
- Male
0301 basic medicine
Microbiology (medical)
Genotype
[SDV]Life Sciences [q-bio]
viruses
Hepacivirus
Hepatitis C virus
030106 microbiology
Viral Nonstructural Proteins
medicine.disease_cause
Antiviral Agents
DNA sequencing
Virus
03 medical and health sciences
chemistry.chemical_compound
symbols.namesake
0302 clinical medicine
Drug Resistance, Viral
medicine
Humans
Pharmacology (medical)
Treatment Failure
030212 general & internal medicine
NS5B
Sanger sequencing
biology
High-Throughput Nucleotide Sequencing
virus diseases
General Medicine
Nucleic acid amplification technique
Middle Aged
biology.organism_classification
Hepatitis C
Virology
digestive system diseases
3. Good health
Infectious Diseases
Amino Acid Substitution
chemistry
symbols
Female
Nucleic Acid Amplification Techniques
Subjects
Details
- ISSN :
- 09248579
- Volume :
- 53
- Database :
- OpenAIRE
- Journal :
- International Journal of Antimicrobial Agents
- Accession number :
- edsair.doi.dedup.....dda7c62792e1e83747aab21b5a879298