Long term persistence of NS5A inhibitor-resistant hepatitis C virus in patients who failed daclatasvir and asunaprevir therapy.

摘要: Although interferon-free antiviral treatment is expected to improve of hepatitis C, it unclear what extent pre-existing drug-resistant amino acid substitutions influence response therapy. The impact on virological daclatasvir and asunaprevir combination therapy was studied in genotype 1b C virus (HCV)-infected patients. Thirty-one patients were treated with for 24 weeks. Twenty-six achieved sustained (SVR), three experienced viral breakthrough, two relapsed. Direct sequencing analysis HCV showed the existence daclatasvir-resistant NS5A-L31M or -Y93H/F variants nine out 30 (30%) prior treatment, while asunaprevir-resistant NS3-D168 mutations not detected any patient. All 21 wild-type NS5A-L31 -Y93 SVR, whereas only four (44%) L31M Y93F/H SVR (P = 0.001). Ultra-deep that failure associated emergence both NS5A-L31/Y93 variants. remained at high frequency through post-treatment weeks 103 170, replaced by all In conclusion, pre-existence NS5A inhibitor-resistant compromised therapy, While emerged during returned wild-type, tended persist absence drug. J. Med. Virol. 87:1913–1920, 2015. © 2015 Wiley Periodicals, Inc.