TY - JOUR
T1 - Baseline hepatitis C virus resistance-associated substitutions present at frequencies lower than 15% may be clinically significant
AU - Perales, Celia
AU - Chen, Qian
AU - Soria, Maria Eugenia
AU - Gregori, Josep
AU - Garcia-Cehic, Damir
AU - Nieto-Aponte, Leonardo
AU - Castells, Lluis
AU - Imaz, Arkaitz
AU - Llorens-Revull, Meritxell
AU - Domingo, Esteban
AU - Buti, Maria
AU - Esteban, Juan Ignacio
AU - Rodriguez-Frias, Francisco
AU - Quer, Josep
PY - 2018/1/1
Y1 - 2018/1/1
N2 - © 2018 Perales et al. Background: Controversy is ongoing about whether a minority mutant present at frequencies below 15% may be clinically relevant and should be considered to guide treatment. Methods: Resistance-associated substitution (RAS) studies were performed in patients before and at failure of antiviral treatments using Next-generation hepatitis C virus (HCV) sequencing (NGS). Results: We have found two patients with genotype 1a infection having RAS in 3.5%–7.1% of the viral population at baseline that were selected during ledipasvir + sofosbuvir treatment. Co-selection of RAS located in a region not directly affected by the antiviral treatment also occurred. This observation calls into question, the recommendations to guide RAS-based direct-acting antiviral (DAA) treatment only when RAS are present in >15% of the sequences generated. Conclusion: Our results suggests that RAS study should include all three HCV DAA target proteins and minority mutants should be considered as clinically relevant.
AB - © 2018 Perales et al. Background: Controversy is ongoing about whether a minority mutant present at frequencies below 15% may be clinically relevant and should be considered to guide treatment. Methods: Resistance-associated substitution (RAS) studies were performed in patients before and at failure of antiviral treatments using Next-generation hepatitis C virus (HCV) sequencing (NGS). Results: We have found two patients with genotype 1a infection having RAS in 3.5%–7.1% of the viral population at baseline that were selected during ledipasvir + sofosbuvir treatment. Co-selection of RAS located in a region not directly affected by the antiviral treatment also occurred. This observation calls into question, the recommendations to guide RAS-based direct-acting antiviral (DAA) treatment only when RAS are present in >15% of the sequences generated. Conclusion: Our results suggests that RAS study should include all three HCV DAA target proteins and minority mutants should be considered as clinically relevant.
KW - Antiviral resistance
KW - HCV
KW - Minority mutants
KW - NGS
U2 - https://doi.org/10.2147/IDR.S172226
DO - https://doi.org/10.2147/IDR.S172226
M3 - Article
C2 - 30519058
VL - 11
SP - 2207
EP - 2210
JO - Infection and Drug Resistance
JF - Infection and Drug Resistance
SN - 1178-6973
ER -