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Direct-acting antiviral (DAA) therapies have revolutionised the treatment of hepatitis C virus (HCV). The financial cost of DAAs however is significant, and first generation protease inhibitors (PIs) also require frequent monitoring of viral RNA levels to guide treatment. In this context, we examined the relevance of HCV antigen testing to evaluate the potential role in monitoring virological response to HCV antiviral treatment with the PI-based triple therapies, telaprevir (TVR) and boceprevir (BOC). Chronic HCV-infected individuals (n = 152) enrolled in the Irish Hepatitis C Outcomes Research Network (ICORN) study were prospectively analysed for baseline markers and the early viral kinetics associated with SVR. The sustained virological response (SVR) rates in the cohort receiving TVR and BOC were 87.3% and 73.8%, respectively. Baseline factors associated with successful outcome in TVR therapy were age ( P  = 0.0098),  IFNL3  genotype ( P  = 0.0330) and viral load ( P  = 0.0456). RNA level at week 4 ( P  = 0.0068) and viral antigen negativity at week 2 ( P  = 0.0359) were predictive of SVR for TVR-based therapy. In BOC therapy, prior interferon treatment ( P  = 0.0209) and  IFNL3  genotype ( P  = 0.0410) were baseline predictors of SVR. Evidence of viraemia based either on viral RNA or antigen at week 4 predicted SVR in these patients. Our data showed that rapid decline of HCV antigen to negative level at week 2 in TVR treatment and <0.96 log fmol/l in BOC treatment after commencement of PI triple therapy were associated with SVR. HCV antigen measurement should be considered as a potential alternative for monitoring treatment response during DAA-based regimens.

The Role of Hepatitis C Virus Core Antigen Testing in the Era of Direct Acting Antiviral Therapies: What We Can Learn from the Protease Inhibitors