Success of Chronic HCV GT1 Retreatment After Failed DAA Therapy

A combination of ombitasvir/paritaprevir/ritonavir and dasabuvir (3D) with sofosbuvir (SOF) and ribavirin (RBV) is highly efficacious for the retreatment of patients with hepatitis C virus (HCV) subtype 1b infection, with or without cirrhosis, who did not experience therapeutic success with previous direct-acting antiviral (DAA) treatment, according to a retrospective study published in the Journal of Viral Hepatitis.

Although the use of DAAs in patients with chronic HCV genotype 1 infection results in sustained virologic response (SVR) rates of 95% to 97%, a sizable percentage of patients still experience virologic failure. The recommendations for retreatment indicate the use of drugs from other classes that do not have cross-resistance with the drugs that have been used previously, and prolonging the earlier retreatment regimens, with or without the addition of RBV.

Researchers observed 17 patients with HCV subtype 1b in whom previous DAA treatment failed, including 13 patients (76.5%) with liver cirrhosis, 12 patients (70.6%) who previously received first-generation DAAs (ledipasvir or daclatasvir), and 5 patients (29.4%) who required 3 rounds of treatment using both first- and second-generation (velpatasvir) DAAs.

All patients were retreated with 3D+SOF+RBV, and the observed sustained virologic response at 12 weeks after treatment (SVR₁₂) rate was 94.1% (16/17 patients) overall. Although retreatment with 3D+SOF+RBV was highly effective and safe in these patients, fibrosis stage, baseline presence of NS5A resistance-associated substitutions mutations, and the generation of previously used NS5A inhibitors may have affected the probability of achieving SVRat 12 weeks post-treatment.

Results demonstrated that F0-F2 fibrosis, single mutations, and failure of first-generation treatments only were associated with 100% SVR at 12 weeks post-treatment; higher grades of fibrosis, double mutations, and second-generation treatment failure SVR at 12 weeks post-treatment ranged from 80% to 92.3%.

The study authors concluded, “we have demonstrated high efficacy of 3D+SOF+RBV for retreatment of patients with HCV subtype 1b infection, with or without cirrhosis, who failed previous DAA treatment.” However, further studies in a larger population are warranted to further confirm and investigate the predictive value of these baseline factors.

Reference

Fedorchenko SV, Martynovych T, Klimenko Z, Yanchenko V, Solianyk I. Retreatment of patients with chronic hepatitis C, subtype 1b and cirrhosis, who failed previous direct acting antiviral therapy including first- and second-generation NS5A inhibitors with ombitasvir/ paritaprevir/ ritonavir, dasabuvir + sofosbuvir + ribavirin [published online January 2, 2020]. J Viral Hepat. doi:10.1111/jvh.13254.