Back to Search
Start Over
Hepatitis C virus early kinetics and resistance-associated substitution dynamics during antiviral therapy with direct-acting antivirals
- Source :
- Journal of Viral Hepatitis. 25:1515-1525
- Publication Year :
- 2018
- Publisher :
- Wiley, 2018.
-
Abstract
- The emergence of resistance-associated substitutions (RASs) can compromise the high efficacy of direct-acting antivirals (DAAs). Little is known about RASs selection at very early time points during DAA treatment. Therefore, we analyzed the potential emergence of RASs immediately after therapy initiation. Samples of 71 patients treated with different DAAs were collected at baseline, during therapy (hours 4 and 8; days 1-7; weeks 2-4) or until target not detected. HCV-RNA levels were determined by qPCR, and RASs were detected by deep sequencing. Sixty-three (89%) patients achieved a sustained virological response (SVR), 7 (10%) relapsed, and 1 (1%) experienced a breakthrough. Almost all non-SVR (7/8, 88%) showed RASs either at baseline or relapse. High-frequency RASs detected at baseline (Y93H and L159F+C316N) remained detectable at early time points during therapy and reappeared as most prevalent substitutions at relapse. Conversely, emergent RASs at relapse (Q80R, D168E/V, R155K and L31V) were not observed during the first hours-days, before HCV-RNA became undetectable. HCV-RNA decay and genetic evolution of the quasispecies followed a similar pattern during the first hours of therapy in SVR and non-SVR patients. In conclusion, the absence of early RASs selection and the similar dynamics of HCV kinetics and quasispecies in SVR and non-SVR patients after therapy initiation suggest that RASs selection may occur at later stages in the remaining reservoir, where viral populations persist hidden at very low replication levels. Nevertheless, we cannot completely exclude very early selection, when RASs are present below the sensitivity limit of deep sequencing.
- Subjects :
- Adult
Male
0301 basic medicine
medicine.medical_specialty
Sustained Virologic Response
Hepatitis C virus
Hepacivirus
Viral quasispecies
Real-Time Polymerase Chain Reaction
DIRECT ACTING ANTIVIRALS
medicine.disease_cause
Antiviral Agents
Gastroenterology
Deep sequencing
Virological response
03 medical and health sciences
0302 clinical medicine
Recurrence
Genetic Evolution
Virology
Internal medicine
Drug Resistance, Viral
Humans
Medicine
Prospective Studies
Selection, Genetic
Aged
Aged, 80 and over
Hepatology
business.industry
Antiviral therapy
virus diseases
Hepatitis C, Chronic
Middle Aged
Viral Load
digestive system diseases
030104 developmental biology
Infectious Diseases
Amino Acid Substitution
RNA, Viral
Female
030211 gastroenterology & hepatology
Sensitivity limit
business
Subjects
Details
- ISSN :
- 13520504
- Volume :
- 25
- Database :
- OpenAIRE
- Journal :
- Journal of Viral Hepatitis
- Accession number :
- edsair.doi.dedup.....0f9d8afb177ad7a28aa51eea03ffdc74