Ledipasvir plus sofosbuvir as salvage therapy for HCV genotype 1 failures to prior NS5A inhibitors regimens.

There is little information on retreatment efficacy and predictors of the combination of ledipasvir and sofosbuvir (ledipasvir/sofosbuvir) for patients who fail to respond to NS5A inhibitors. NS5A resistance variants are known to persist for long periods after such treatment. Here, we evaluated 54 patients with chronic HCV genotype 1b infection, free of decompensated cirrhosis, and hepatocellular carcinoma, for sustained virological response after 12 weeks (SVR12) of once-daily treatment with 90 mg ledipasvir and 400 mg sofosbuvir. Intention-to-treat analysis showed SVR12 of 70%. Using ultra-deep sequencing, non-responder to ledipasvir/sofosbuvir showed no change in the rates of detection of NS5A and NS5B resistant-variants at re-elevation of viral loads, relative to baseline. According to response to prior treatment, SVR12 rates were 18, 69, 94, and 100% in non response, viral breakthrough, relapse, and discontinuation due to adverse events, respectively. SVR12 rates in non response were significantly lower than those of the others. Multivariate analysis identified response to previous treatment (failure except for non response) and FIB4 index (<3.25) as significant determinants of SVR12. The SVR12 rates were significantly lower in patients with FIB4 index of ≥3.25 and had not responded to prior treatment, relative to others. The specificity, and positive- and negative-predictive values were high for prediction of poor response based on the combination of two predictors. In conclusion, our study indicated that ledipasvir/sofosbuvir is a potentially useful salvage treatment for patients who fail prior NS5A inhibitors-based therapy. Response to prior treatment was an important predictor of retreatment efficacy.