Pre-Existing HCV Variants Resistant to DAAs and Their Sensitivity to PegIFN/RBV in Chinese HCV Genotype 1b Patients.
BACKGROUND
The efficacy of direct-acting antiviral agents (DAAs) could be attenuated by the presence of resistance-associated variants (RAVs). The aim of this study was to investigate the natural prevalence of RAVs among Chinese HCV genotype 1b patients and analyze the efficacy of pegylated interferon (PegIFN)/ribavirin (RBV) therapy in patients with and without RAVs at baseline.


METHODS
Direct sequencing of the HCV NS3, NS5A and NS5B regions was performed in baseline serum samples of 117 DAAs-naïve subjects infected with HCV genotype 1b. The efficacy of PegIFN/RBV therapy in patients with and without RAVs at baseline was analyzed by comparing the response rates between patients with RAVs and patients with wild type virus.


RESULTS
The incidence of RAVs was 8.00% (8/100) in the NS3 region (T54S, n = 1, 1.00%; R117H, n = 5, 5.00%; S122T, n = 1, 1.00%; S174F, n = 1, 1.00%), 29.91% (32/107) in the NS5A region (L28M, n = 12, 11.21%; R30Q, n = 10, 9.35%; L31M, n = 1, 0.93%; P58S, n = 4, 3.74%; Y93H, n = 8, 7.48%) and 98.15% (106/108) in the NS5B region (L159F, n = 1, 0.93%; C316N, n = 103, 95.37%; A421V, n = 6, 5.56%). The response rates to PegIFN/RBV treatment did not differ between patients with or without RAVs in the NS5A region.


CONCLUSIONS
Pre-existing RAVs, including key RAVs, were detected in Chinese DAAs-naïve patients infected with HCV genotype 1b. IFN-based therapy could be a good option for patients with RAVs, especially key RAVs, at baseline.
Department of Infectious Diseases, Peking University First Hospital, Beijing, China.
Yu
Y
Zhang
Department of Infectious Diseases, Peking University First Hospital, Beijing, China.
Ying
Y
Cao
Department of Infectious Diseases, Peking University First Hospital, Beijing, China.
Renwen
R
Zhang
Department of Infectious Diseases, Peking University First Hospital, Beijing, China.
Xiaxia
X
Zhang
Department of Infectious Diseases, Peking University First Hospital, Beijing, China.
Haiying
H
Lu
Department of Infectious Diseases, Peking University First Hospital, Beijing, China.
Chihong
C
Wu
Department of Infectious Diseases, Peking University First Hospital, Beijing, China.
Na
N
Huo
Department of Infectious Diseases, Peking University First Hospital, Beijing, China.
Xiaoyuan
X
Xu
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000627:therapeutic use*; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D002219:Carbamates; D002681:China; D024882:Drug Resistance, Viral / Q000235:genetics*; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D016898:Interferon-alpha / Q000627:therapeutic use*; D007546:Isoquinolines / Q000627:therapeutic use*; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011759:Pyrrolidines; D020365:RNA Helicases / Q000037:antagonists & inhibitors / Q000235:genetics; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use*; D017422:Sequence Analysis, DNA; D012697:Serine Endopeptidases / Q000235:genetics; D013449:Sulfonamides / Q000627:therapeutic use*; D014633:Valine / Q000031:analogs & derivatives; D019562:Viral Load / Q000187:drug effects; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors / Q000235:genetics*; D055815:Young Adult; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; D012324:RNA-Dependent RNA Polymerase
D000998:Antiviral Agents; D002219:Carbamates; D007093:Imidazoles; D016898:Interferon-alpha; D007546:Isoquinolines; D011092:Polyethylene Glycols; D011759:Pyrrolidines; D020365:RNA Helicases; D011994:Recombinant Proteins; D012254:Ribavirin; D012697:Serine Endopeptidases; D013449:Sulfonamides; D014633:Valine; D017361:Viral Nonstructural Proteins; C060028:NS3 protein, flavivirus; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase; C549273:daclatasvir; C100416:peginterferon alfa-2a; C571889:asunaprevir