Abstract
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.
Highlights
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
Our current study demonstrated that the global prevalence of DAA RAVs was high
This frequency is significantly higher than that observed in the previous study by Kuntzen et al.[17] which reported that HCV genome dominant
Summary
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. Direct-acting antiviral agents (DAAs) have become the new standard of anti-HCV therapy and have shown an extremely high SVR rate[4]. The advantage of DAA based therapy is the ability to directly inhibit specific HCV proteins that are important for HCV replication in hepatocytes, including non-structural(NS)3/4A protease[5], NS5A protein[6] and NS5B polymerase[7]. Several novel anti-HCV compounds have recently been investigated These include: i) the NS3 protease inhibitors Boceprevir, Telaprevir, Paritaprevir and Simeprevir; ii) the NS5A inhibitors Daclatasvir, Ledipasvir and Omitasvir; and iii) the NS5B nucleo(t)ide inhibitor (NI) Sofosbuvir and non-nucleo(t)ide inhibitor (NNI) Dasabuvir. Novel populations that can contain every potential substitution (some of which convey various degrees of resistance to DAAs) are likely created and lost each day[8]
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