African-Americans with hepatitis C virus (HCV) genotype 1 infections have lower ribavirin plasma exposures than Caucasian Americans when treated with weight-based ribavirin plus peginterferon.
However, when they reach plasma exposure thresholds, African-American patients are just as likely to achieve viral responses as Caucasians.
"These results provide important new insights into the basis for the racial disparity in the treatment responses to peginterferon and ribavirin treatment for HCV genotype 1," say Charles Horwell (University of Maryland, Baltimore, USA) and colleagues.
The study included 71 African-Americans and 74 Caucasians who were over 90% adherent to their therapy during the 48-week VIRAHEP-C (viral resistance to antiviral therapy for chronic hepatitis C) trial. Patients received peginterferon alfa-2a 180 µg per week plus ribavirin at 1000 mg for those weighing under 75 kg, or 1200 mg for those weighing 75 kg and over.
Compared with Caucasian patients, African-American patients had significantly lower plasma concentrations of ribavirin at weeks 1,2,and 4, and significantly lower cumulative ribavirin exposure (AUC) during the first 12 weeks. They were significantly less likely to reach a threshold exposure level during the first 7 days.
Overall, 57.8% of African-American patients had a response at week 24 which was significantly fewer compared with 78.1% of Caucasian patients. Similarly, at week 72, only 36.6% showed a sustained viral response compared with 54.8% of Caucasian patients.
Interestingly, however, when patients met ribavirin threshold levels during the first 7 days, there were no significant differences in responses at 24 weeks or 72 weeks between African-American and Caucasian patients (week 24: 77 vs 84%; week 72: 52 vs 60%).
Around 50% of the racial disparity seen in responses to ribavirin is thought to be due to a single nucleotide polymorphism near the IL28B gene locus, explain the authors.
"The present study shows that variability in ribavirin AUC0-7 [AUC during days 0-7] can explain much of the remaining difference between African Americans and Caucasian Americans in peginterferon and weight-based ribavirin treatment efficacy," they say.
Horwell and colleagues say that their study had a larger number of African-Americans than previous studies and had the advantage of only including patients who were highly adherent to their therapy.
"Future studies should determine the importance of ribavirin pharmacokinetic variability to racial disparities in treatment responses to HCVNS3 protease inhibitors and other direct-acting antiviral treatments for HCV," they conclude in the American Journal of Gastroenterology.
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