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Resistance Analyses of Japanese Hepatitis C‐Infected Patients Receiving Sofosbuvir or Ledipasvir/Sofosbuvir Containing Regimens in Phase 3 Studies
Author(s) -
Mizokami M.,
DvorySobol H.,
Izumi N.,
Nishiguchi S.,
Doehle B.,
Svarovskaia E. S.,
DeOertel S.,
Knox S.,
Brainard D. M.,
Miller M. D.,
Mo H.,
Sakamoto N.,
Takehara T.,
Omata M.
Publication year - 2016
Publication title -
journal of viral hepatitis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 100
eISSN - 1365-2893
pISSN - 1352-0504
DOI - 10.1111/jvh.12549
Subject(s) - ns5a , ledipasvir , sofosbuvir , medicine , hepatitis c virus , ns5b , virology , ribavirin , gastroenterology , hepatitis c , hepacivirus , virus
Summary High rates of sustained virologic response ( SVR ) has been achieved in Japanese patients with chronic hepatitis C virus ( HCV ) genotype ( GT )1 and GT 2 infection treated with ledipasvir/sofosbuvir ( LDV / SOF ) ±ribavirin ( RBV ) and SOF + RBV , respectively. We evaluated the effect of baseline HCV NS 5A and NS 5B resistance‐associated variants ( RAV s) on treatment outcome and characterized variants at virologic failure. Baseline deep sequencing for NS 5A and NS 5B genes was performed for all GT 1 patients. Deep sequencing of NS 5A ( GT 1 only) and NS 5B ( GT 1 and GT 2) was performed for patients who failed treatment or discontinued early with detectable HCV RNA (i.e., >25 IU / mL ). In patients with HCV GT 1 infection, 22.3% ( GT 1a: 2/11; GT 1b: 74/330) had ≥1 baseline NS 5A RAV . The most frequent NS 5A RAV s in GT 1b were Y93H (17.9%, 59/330) and L31M (2.4%, 8/330). Despite the presence of NS 5A RAV s at baseline, 100% and 97% of patients achieved SVR 12, compared with 100% and 99% for those with no NS 5A RAV s with LDV / SOF and LDV / SOF + RBV , respectively. All patients with NS 5B RAV s at baseline achieved SVR 12. Of the 153 patients with GT 2 infection ( GT 2a 60.1%, GT 2b 39.9%), 3.3% (5/153) experienced viral relapse. No S282T or other NS 5B RAV s were detected at baseline or relapse; no change in susceptibility to SOF or RBV was observed at relapse. In conclusion, LDV / SOF and SOF + RBV demonstrate a high barrier to resistance in Japanese patients with HCV GT 1 and GT 2 infection. The presence of baseline NS 5A RAV s did not impact treatment outcome in GT 1 Japanese patients treated with LDV / SOF for 12 weeks.