The efficacy of directly acting antiviral agents in interferon-free regimens for the treatment of chronic hepatitis C infections needs to be evaluated in different populations.
Dr Anuoluwapo Osinusi and colleagues from Maryland, USA determined the efficacy and safety of sofosbuvir with weight-based or low-dose ribavirin among a population with unfavorable treatment characteristics.
Single-center, randomized, 2-part, open-label phase 2 study involving 60 treatment-naive patients with hepatitis C virus (HCV) genotype 1 enrolled at the National Institutes of Health.
In the study’s first part, 10 participants with early to moderate liver fibrosis were treated with 400 mg/d of sofosbuvir and weight-based ribavirin for 24 weeks.
|The most frequent adverse events included headaches|
|Journal of the American Medical Association|
In the second part, 50 participants with all stages of liver fibrosis were randomized 1:1 to receive 400 mg of sofosbuvir with either weight-based or low-dose 600 mg/d of ribavirin for 24 weeks.
The team's primary study end point was the proportion of participants with undetectable HCV viral load 24 weeks after treatment completion.
In the first part of the study, 9 participants achieved sustained virological response rates.
In the second part, 7 participants in the weight-based group, and 10 in the low-dose group relapsed after treatment completion leading to sustained virological response rates of 68% in the weight-based group, and 48% in the low-dose group.
The team found that 20 individuals that participated in a pharmacokinetic-viral kinetic substudy, demonstrated a slower loss rate of infectious virus in relapsers than in participants who achieved sustained virological response rates.
The researchers observed that the most frequent adverse events were headache, anemia, fatigue, and nausea.
There were 7 grade 3 events including anemia, neutropenia, nausea, hypophosphatemia, and cholelithiasis or pancreatitis.
No one discontinued treatment due to adverse events.
Dr Osinusi's team concludes, "In a population of patients with a high prevalence of unfavorable traditional predictors of treatment response, a 24-week regimen of sofosbuvir and weight-based or low-dose ribavirin resulted in sustained virological response rates of 68% and 48%, respectively."