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New study: HCV and racial disparities in response to antiviral therapy
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Abstract: This study will evaluate sustained viral response rates, and tests for host and genetic differences between whites and African-Americans to try to figure out why African-Americans appear to have less response than whites to interferon+ribavirin therapy. Sites where the study is held are listed below if you are interested in participating. Study participants will receive Pegasys 180 mcg + ribavirin 1000/1200 mg per day.
VIRAHEP-C is a multicenter, collaborative phase III clinical trial sponsored by NIH-NIDDK that has begun testing the hypothesis that African-Americans with chronic hepatitis C respond less well to antiviral therapy than Caucasian patients. This open-label trial will evaluate the relative efficacy of pegylated interferon and ribavirin in African-American and Caucasian treatment cohorts.
"Major advances have occurred over the last decade in the field of antiviral therapy for chronic hepatitis C. Unfortunately, response to therapy has not been uniformly favorable," said Dr. Michael W. Fried, Associate Professor of Medicine and Director of Clinical Hepatology at the University of North Carolina at Chapel Hill.
Fried, a Principal Investigator in the trial, noted that sustained response rates have improved to nearly 40% with interferon and ribavirin combination therapy, compared with 10% to 15% for patients treated with interferon alone. However, secondary analyses of large databases derived from clinical trials of various antiviral agents suggest that racial disparities may exist in response to therapy for HCV. In one such analysis, for example, sustained virological response occurred in only 2% of African Americans in the trial, compared with 12% of Caucasian participants.
However, these trials were not designed to study race as a factor in response to therapy. Moreover, few African-Americans have been included as study subjects, despite the high prevalence of HCV in this population.
The new trial will enroll a total of 400 patients, equally divided between African- American and Caucasian, at 8 clinical centers in the United States.
All participants will be HCV genotype 1 with quantifiable (600 IU/mL) HCV RNA. This genotype accounts for approximately 75% of HCV infections in the United States and affects 91% of African-Americans with HCV compared with 67% of Whites. This genotype is also more difficult to treat, said Dr. Rajender Reddy, Director of Hepatology and Medical Director of Liver Transplantation at the University of Pennsylvania. "Whether the lower treatment response rate (among African Americans) is related to a higher prevalence of genotype 1 or is due to other factors is unclear, but it appears to be partly genotype driven."
Participants will be treated for 48 weeks with pegylated interferon alpha-2a 180 mcg/week plus ribavirin 10001200 mg/day. They will be followed-up for an additional 48 weeks after cessation of therapy. Sustained virological response rates (undetectable HCV RNA in serum 24 weeks posttreatment) and durable sustained virological response rates (undetectable HCV RNA in serum 48 weeks posttreatment) between the 2 treatment cohorts will be compared to determine differences in treatment response.
Pretreatment variables such as gender, history of alcohol use, HCV RNA levels, and hepatic histology will be studied to determine possible factors associated with sustained virological response and how they may differ between the treatment groups. Potential mechanisms of antiviral resistance will be explored in ancillary studies using serum and peripheral blood mononuclear cells obtained from participants at various times in the trial. Viral kinetics, immunological responses, measures of interferon signaling pathways, and host and viral genetics will be evaluated in relation to treatment response.
VIRAHEP-C participating centers are: Beth-Israel Deaconess Medical Center, Boston; New York-Presbyterian Medical Center, NYC; University of California San Francisco; University of Illinois, Chicago; University of Maryland, Baltimore; University of Miami, Florida; University of Michigan, Ann Arbor; University of North Carolina at Chapel Hill.
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