Daclatasvir–sofosbuvir combo effective in chronic HCV infection

Jan 24 2014

Research shows that the combination of daclatasvir and sofosbuvir leads to high rates of sustained virologic response in patients with chronic hepatitis C virus (HCV) infection, including those who have not responded to previous therapy.

The study, published in the New England Journal of Medicine, also found the combination was effective in patients with characteristics typically leading to unfavorable outcomes, including those with HCV genotypes 1a and 3, and the non-CC IL28B genotype.

The researchers, led by Mark Sulkowski (Johns Hopkins University School of Medicine, Baltimore, Maryland, USA), studied 211 patients, 44 of whom were infected with HCV genotype 2 or 3 and 167 with genotype 1, including 41 who had not responded to protease inhibitors.

Patients were randomly assigned to receive sofosbuvir for a week followed by daclatasvir and sofosbuvir for 23 weeks, daclatasvir and sofosbuvir for 24 weeks, or daclatasvir, sofosbuvir, and ribavirin for 24 weeks.

Overall, 91% of patients infected with genotype 2 or 3 had a sustained virologic response (HCV RNA <25 IU/mL) 12 weeks after the end of treatment, as did 93% after 24 weeks. One patient with genotype 3 infection experienced virologic breakthrough during treatment and had to be given rescue therapy.

Among patients with genotype 1 infections, sustained virologic response was observed in 98% at 12 weeks after the end of treatment, and no patient had virologic breakthrough during treatment.

Rates of sustained virologic response were similar across subgroups including genotype 1a and 1b infection (98 and 100%), IL28B genotype (CC: 93%; non-CC: 98%), race (White: 97%; Black: 96%; Other: 90%), concurrent ribavirin treatment (with: 94%; without: 98%), and history of treatment failure with protease inhibitors (98%).

Additionally, among the 126 patients with previously untreated genotype 1 infection, 95% had a sustained virologic response and none showed any evidence of daclatasvir-resistant or sofosbuvir-resistant variants.

Sulkowski et al say that the findings provide “proof of concept” that a sustained virologic response can be obtained in patients in whom previous treatment with protease inhibitors has failed, including those with variants conferring resistance.

Additionally, they note that, given the similar response rates among patients who did and did not receive ribavirin, a ribavirin-sparing regime may be possible with the new drug combination, avoiding the side effects and inconvenience of the drug.

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