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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 F0–F2) 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.
The Friends of AIDS Foundation is
dedicated to enhancing the quality of life for HIV positive individuals and
empowering people to make healthy choices to prevent the spread of the HIV
virus. To learn more about The Friends of AIDS Foundation, please visit: http://www.friendsofaids.org.
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