Patients chronically infected with hepatitis C virus (HCV) genotype 2 or 3 for whom
treatment with peginterferon is not an option, or who have not had a response to prior
interferon treatment, currently have no approved treatment options. In phase 2 trials,
regimens including the oral nucleotide polymerase inhibitor sofosbuvir have shown
efficacy in patients with HCV genotype 2 or 3 infection.
We conducted two randomized, phase 3 studies involving patients with chronic HCV genotype
2 or 3 infection. In one trial, patients for whom treatment with peginterferon was
not an option received oral sofosbuvir and ribavirin (207 patients) or matching placebo
(71) for 12 weeks. In a second trial, patients who had not had a response to prior
interferon therapy received sofosbuvir and ribavirin for 12 weeks (103 patients) or
16 weeks (98). The primary end point was a sustained virologic response at 12 weeks
after therapy.
Among patients for whom treatment with peginterferon was not an option, the rate of
a sustained virologic response was 78% (95% confidence interval [CI], 72 to 83) with
sofosbuvir and ribavirin, as compared with 0% with placebo (P<0.001). Among previously
treated patients, the rate of response was 50% with 12 weeks of treatment, as compared
with 73% with 16 weeks of treatment (difference, -23 percentage points; 95% CI, -35
to -11; P<0.001). In both studies, response rates were lower among patients with genotype
3 infection than among those with genotype 2 infection and, among patients with genotype
3 infection, lower among those with cirrhosis than among those without cirrhosis.
The most common adverse events were headache, fatigue, nausea, and insomnia; the overall
rate of discontinuation of sofosbuvir was low (1 to 2%).
In patients with HCV genotype 2 or 3 infection for whom treatment with peginterferon
and ribavirin was not an option, 12 or 16 weeks of treatment with sofosbuvir and ribavirin
was effective. Efficacy was increased among patients with HCV genotype 2 infection
and those without cirrhosis. In previously treated patients with genotype 3 infection,
16 weeks of therapy was significantly more effective than 12 weeks. (Funded by Gilead
Sciences; POSITRON and FUSION ClinicalTrials.gov numbers, NCT01542788 and NCT01604850,
respectively.).