HealthDay News — Among patients with chronic hepatitis C virus (HCV) who have unfavorable treatment characteristics a two-drug interferon-free regimen was effective at maintaining a sustained virologic response, researchers found.
A 24-week combination regimen of sofosbuvir and weight-based or low-dose ribavirin was associated with a sustained virologic response to treatment of 68% and 48%, respectively, among patients deemed unlikely to respond to treatment, Anuoluwapo Osinusi, MD, MPH, from the National Institutes of Health in Bethesda, Md., and colleagues reported in the Journal of the American Medical Association.
A separate, smaller group of patients with early to moderate liver fibrosis had a 90% sustained virologic response at 24 weeks to sofosbuvir with weight-based ribavirin, the researchers found.
Hepatitis C is common in urban areas with large populations of patients that have unfavorable predictors of treatment response, such as black race, advanced liver fibrosis, IL28B CT or TT genotypes high baseline viral loads and prior treatment experience, according to background information in the study.
Although recent studies have shown favorable outcomes with interferon-free, direct-acting antiviral regimens, data are not available on populations with poor treatment responses.
So Osinusi and colleagues studied the safety and efficacy of a sofosbuvir and weight-based or low-dose ribavirin regimen in 60 patients with hepatitis C who were in various stages of liver fibrosis.The primary endpoint was undetectable viral load at 24 weeks after treatment completion.
Participants had hepatitis C genotype 1 infections, chronic disease confirmed with liver biopsy, were treatment-naive and hepatitis B and HIV negative. Absolute neutrophil counts were 750 cells/uL or greater, platelet counts were 50,000 cells/uL and hemogloblin was 11 g/dL or greater in women and 12 g/dL in men.
In the first phase of the study, 10 patients with early to moderate fibrosis were treated with sofosbuvir and weight-based ribavirin (400 mg in the morning and 600 mg in the evening for patients that weighed less than 75 kg, or 600 mg twice a day for patients that weighted 75 kg or more).
The remaining 50 participants (at all stages of liver fibrosis) were randomly assigned one-to-one to sofosbuvir (400 mg/day) and either weight-based or low-dose (600 mg/day) ribavirin for 24 weeks.
The researchers measured viral loads via plasma RNA and monitored adherence by pill count at each visit. The majority of participants were black (83%) and male (66%), and 48% were obese. By disease characteristic, 81% had the IL28 CT or TT genotype, 70% had the GT-1a genotype, 23% had advanced liver disease, and 62% had a baseline viral RNA level above 800,000.
The researchers found that, of the 10 patients with early to moderate fibrosis, 90% had a sustained virologic response (SVR; undetectable HCV viral load) at the end of the study.
Of the 50 patients in the remaining group, 28% of the weight-based group and 40% of the low-dose group relapsed, giving an SVR of 68% and 48%, respectively. Relapse was significantly more likely in males (odds ratio 6.09, 95% CI 1.17-31.6), patients with advanced fibrosis (OR 4.27, 95% CI 1.10-16.54) and among patients with a baseline viral RNA load of 800,000 IU/mL (OR 5.74, 95% CI 1.35-24.38).
A pharmacokinetic study showed that relapsers had a slower rate of loss of infectious virus (clearance 3.57 daily versus 5.60 daily, P=0.009). Headache, anemia, fatigue and nausea were the most common adverse events. Although there were seven grade 3 events, there were no deaths or discontinuations due to adverse events.
Study limitations included small sample size, the researchers acknowledged.