Fiona McPhee
Bristol-Myers Squibb Co, USA
Title: Impact of baseline NS5A polymorphisms on sustained virologic response in patients infected with HCV treated with daclatasvir-based regimens
Biography
Biography: Fiona McPhee
Abstract
The most prevalent Hepatitis C virus (HCV) genotype (GT) globally is GT-1 (46%) with GT-1b being the most common subtype (22%). In Europe, GT-1b accounts for approximately 50% of all HCV cases. Daclatasvir (DCV)-based regimens are approved in many countries globally, including Europe, United States and Asia, for the treatment of HCV. In patients infected with HCV, response rates to DCV-based regimens can depend on the regimen, GT, and pre-treatment nonstructural 5A (NS5A) resistance-associated polymorphisms (RAPs) to DCV. The effects of NS5A RAPs at L31 or Y93H on sustained virologic response (SVR) to treatment with DCV+asunaprevir (ASV; NS3 protease inhibitor) for 24 weeks or treatment with DCV+sofosbuvir (SOF; NS5B inhibitor) for 12 weeks were explored using pooled data from clinical studies in HCV GT-1b-infected patients. SVR with versus without baseline NS5A RAPs was compared by age (<65 vs.>65 years), cirrhosis status, and baseline viral load. Baseline NS5A sequences were available for 1224 GT-1b patients treated with DCV+ASV and 28 GT-1b patients treated with DCV+SOF. NS5A RAPs at L31 or Y93H were observed pretreatment in 4% or 11% of patients, respectively. The overall SVR rate in DCV+ASV-treated patients without NS5A RAPs at L31 or Y93H was 95% compared to 40% with these RAPs. SVR rates in DCV+ASV treated patients without RAPs was high irrespective of cirrhosis, age, or baseline viral load. The overall SVR rate in DCV+SOF-treated patients was 100%. These results will be discussed.