March 21, 2013
Researchers recently reported that a simple 24-week oral regimen of Gilead Sciences' nucleotide analogue hepatitis C virus (HCV) polymerase inhibitor sofosbuvir and full-dose ribavirin cured approximately 70 percent of previously untreated individuals with HCV genotype 1. Many of the participants had factors predictive of poor response. Anu Osiniusi of the National Institute of Allergy and Infectious Diseases and colleagues tested a two-drug, interferon-free treatment regimen in a small phase IIa study of difficult-to-treat patients in inner-city neighborhoods of Washington, D.C.
The SPARE study, which began in 2011, evaluated sofosbuvir plus ribavirin. The study was conducted in two parts. In Part 1, researchers treated 10 people with absent to-moderate liver fibrosis (stage F0F2) for 24 weeks with 400 milligrams once-daily of sofosbuvir plus weight-based ribavirin at 1,000 milligrams per day (mg/day) if weight was less than 75 kilograms (kg), or 1,200 mg/day if 75 kg or more. In part 2, researchers randomly assigned 50 people with all stages of liver disease to sofosbuvir with either weight-based ribavirin or a lower fixed dose of 600 mg/day regardless of weight. Seventy percent of the subjects chosen for the second part of the study were men; the median age was 54 years; and 80 percent of the subjects were African-American. African Americans usually respond poorly to interferon. Approximately 70 percent of participants had the more difficult-to-treat HCV sub-type 1a, and approximately 60 percent had a high baseline viral load.
In Part 1, there was a 90-percent sustained virological response rate at 12 weeks post-treatment, rising to 100 percent in a modified analysis of all participants treated for at least 8 weeks. In Part 2, HCV RNA declined rapidly with almost all participants reaching undetectable viral load by the fourth week. Response rate remained high at 24 weeks of treatment. Some participants started to relapse soon after stopping treatment, especially in the low-dose ribavirin group. Sustained response rates at the fourth week post-treatment (SVR 4) were 72 and 56 percent, respectively. A few later relapses occurred resulting in SVR 12 rates of 68 and 48 percent. Viral decline after starting treatment was slower among people who eventually relapsed compared with sustained responders, with clearance occurring in 3.6 vs 5.6 days on average. Host and viral factors associated with relapse included lower baseline viral load, male sex, and using low-dose rather than weight-based ribavirin. Having worse fibrosis or cirrhosis seemed to predict poorer response.
Sofosbuvir plus ribavirin was generally safe and well tolerated, with no serious adverse events, drop-outs due to side-effects, or deaths in either group. Laboratory abnormalities differed according to ribavirin dose. The researchers concluded that, in an inner-city population of HCV genotype 1 subjects with negative treatment predictors, an interferon-free regimen of sofosbuvir with weight-based ribavirin was effective in achieving high SVR rates.
This study was presented at the 20th Conference on Retroviruses and Opportunistic Infections in Atlanta, Georgia.