Global prevalence of pre-existing HCV variants resistant to direct-acting antiviral agents (DAAs): mining the GenBank HCV genome data

• Published in: Scientific reports Vol. 6; no. 1; p. 20310
• Main Authors: Chen, Zhi-wei, Li, Hu, Ren, Hong, Hu, Peng
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 04-02-2016; Nature Publishing Group
• Subjects: 631/1647; 692/4020; Antiviral agents; Antiviral Agents - pharmacology; Data processing; Databases, Genetic; Drug Resistance, Viral - drug effects; Drug Resistance, Viral - genetics; Gene Frequency; Genomes; Genotype; Geography; Hepacivirus - drug effects; Hepacivirus - genetics; Hepacivirus - metabolism; Hepatitis C; Hepatitis C - epidemiology; Hepatitis C - virology; Humanities and Social Sciences; Humans; Interferon; multidisciplinary; Prevalence; Protease inhibitors; Protease Inhibitors - pharmacology; Proteinase inhibitors; Science; Viral Nonstructural Proteins - antagonists & inhibitors; Viral Nonstructural Proteins - genetics; Viral Nonstructural Proteins - metabolism
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep20310

Direct-acting antiviral agents (DAAs) against hepatitis C virus (HCV) proteins open a whole new era for anti-HCV therapy, but DAA resistance associated variants (RAVs) could jeopardize the effectiveness of DAAs. We reported the global prevalence of DAA RAVs using published GenBank data. 58.7% of sequences (854/1455) harbored at least one dominant resistance variant and the highest RAV frequency occurred in Asia (74.1%), followed by Africa (71.9%), America (53.5%) and Europe (51.4%). The highest RAV frequency was observed in genotype (GT) 6 sequences (99%), followed by GT2 (87.9%), GT4 (85.5%), GT1a (56%), GT3 (50.0%) and GT1b (34.3%). Furthermore, 40.0% and 29.6% of sequences were detected RAVs of non-structural (NS) 5A inhibitors and NS3 protease inhibitors, respectively. However, RAVs to NS5B nucleo(t)ide inhibitor (NI) and NI-based combinations were uncommon (<4% of sequences). As expected, combinations of multiple RAVs to the IFN-free regimens recommended by current guidelines were rarely detected (0.2%–2.0%). Our results showed that the overall global prevalence of DAA RAVs was high irrespective of geography or genotype. However, the NI-based multi-DAA regimens had a low RAV prevalence, suggesting that these regimens are the most promising strategies for cure of the long-term HCV infection.