Sofosbuvir/Velpatasvir Effective Despite HCV Resistance-Associated Variants

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pink pills on blue background
The impact of baseline resistance-associated substitutions on hepatitis C treatment outcomes was evaluated in patients treated with sofosbuvir/velpatasvir.

A fixed dose combination of sofosbuvir/velpatasvir taken once daily for 12 weeks results in high sustained virologic response rates in patients infected with hepatitis C (HCV) across genotypes regardless of baseline resistance to pretreatment nonstructural protein 5a (NS5A) inhibitor therapy, according to study findings published in the Journal of Hepatology.

The study analyzed a total of 6 phase 3 clinical trials examining patients chronically infected with HCV genotypes 1-6 who received fixed dose sofosbuvir/velpatasvir. Particular focus was placed on patients with baseline resistance to NS5A nonstructural protein 5b (NS5B) inhibitor therapy. Of the 1778 patients included in the study, 28% (range 9% to 61%, depending upon HCV genotype) had NS5A class resistance-associated substitutions (RASs).

Investigators found that NS5A class RASs had no significant impact on the probability of achieving undetectable HCV at 12 months with the treatment regimen. The rate of freedom from HCV at 12 months of treatment in patients with NS5A class RASs vs genotype 1a and genotype 1b infection was 100% and 97%, respectively.

In addition, undetectable HCV at the end of treatment was 100% in patients infected with HCV genotypes 2, 4, 5, and 6. There was no difference in patients infected with genotype 3 HCV with or without baseline NS5A class RASs with regard to the sustained virologic response rate (93% and 98%, respectively).

Overall, the virologic failure rate associated with sofosbuvir/velpatasvir therapy was 1.1%. The majority of patients in virologic failure (17/20) had single NS5A class resistance.

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The findings from this study warrant further analysis in a randomized placebo-controlled trial in order to derive more conclusive evidence for the success rate of this therapeutic regimen in the presence of NS5A class resistance.

Data generated from these trials demonstrate “the high barrier to resistance of this regimen for the treatment of chronic HCV across all genotypes in [the] vast majority of patients.”

This study was funded by Gilead Sciences.


Hezode C, Reau N, Svarovskaia ES, et al. Resistance analysis in patients with genotype 1-6 HCV infection treated with sofosbuvir/velpatasvir in the phase 3 studies [published online December 5, 2017]. J Hepatol. doi:10.1016/j.jhep.2017.11.032