Naturally occurring mutations associated with resistance to HCV NS5B polymerase and NS3 protease inhibitors in treatment-naïve patients with chronic hepatitis C

• Published in: Virology journal Vol. 12; no. 1; p. 186
• Main Authors: Costantino, Angela, Spada, Enea, Equestre, Michele, Bruni, Roberto, Tritarelli, Elena, Coppola, Nicola, Sagnelli, Caterina, Sagnelli, Evangelista, Ciccaglione, Anna Rita
• Format: Journal Article
• Language: English
• Published: England BioMed Central 14.11.2015
• Subjects: Adult; Aged; Aged, 80 and over; Antiviral Agents - pharmacology; Drug Resistance, Viral; Emigrants and Immigrants; Hepacivirus - drug effects; Hepacivirus - genetics; Hepacivirus - isolation & purification; Hepatitis C, Chronic - epidemiology; Hepatitis C, Chronic - virology; Humans; Italy; Male; Middle Aged; Mutation, Missense; Polymorphism, Genetic; Protease Inhibitors - pharmacology; RNA, Viral - blood; RNA, Viral - genetics; RNA, Viral - isolation & purification; Sequence Analysis, DNA; Short Report; Sofosbuvir - pharmacology; Viral Nonstructural Proteins - genetics; Young Adult; Italy
• DOI: 10.1186/s12985-015-0414-1
• ISSN: 1743-422X

The detection of baseline resistance mutations to new direct-acting antivirals (DAAs) in HCV chronically infected treatment-naïve patients could be important for their management and outcome prevision. In this study, we investigated the presence of mutations, which have been previously reported to be associated with resistance to DAAs in HCV polymerase (NS5B) and HCV protease (NS3) regions, in sera of treatment-naïve patients. HCV RNA from 152 naïve patients (84 % Italian and 16 % immigrants from various countries) infected with different HCV genotypes (21,1a; 21, 1b; 2, 2a; 60, 2c; 22, 3a; 25, 4d and 1, 4k) was evaluated for sequence analysis. Amplification and sequencing of fragments in the NS5B (nt 8256-8640) and NS3 (nt 3420-3960) regions of HCV genome were carried out for 152 and 28 patients, respectively. The polymorphism C316N/H in NS5B region, associated with resistance to sofosbuvir, was detected in 9 of the 21 (43 %) analysed sequences from genotype 1b-infected patients. Naturally occurring mutations V36L, and M175L in the NS3 protease region were observed in 100 % of patients infected with subtype 2c and 4. A relevant proportion of treatment naïve genotype 1b infected patients evaluated in this study harboured N316 polymorphism and might poorly respond to sofosbuvir treatment. As sofosbuvir has been approved for treatment of HCV chronic infection in USA and Europe including Italy, pre-treatment testing for N316 polymorphism on genotype 1b naïve patients should be considered for this drug.