Jul 28 2004
A new study reveals the highest efficacy rates ever reported among patients co-infected with hepatitis C and HIV treated with pegylated interferon and ribavirin.
The study found that the drug combination of Pegasys(R) (peginterferon alfa-2a) and Copegus(R) (ribavirin) was much more effective than the previous generation of hepatitis C therapy standard interferon and ribavirin. Efficacy was measured as the sustained virological response (SVR) rate, which is defined by the absence of detectable HCV RNA in the serum for at least six months after treatment.
Since 2001, pegylated interferon, which is long-acting and injected weekly, has been approved for treatment alone or in combination with ribavirin. Successful treatment can eradicate the virus. Treatment can also slow disease progression, improve histology, and reduce the risk of liver cancer. Combination therapy is most effective in patients with HCV genotypes 2 and 3, which represent about 25 percent of patients in the United States. The most common genotypes, 1a and 1b, which affect about 75 percent of patients in the United States, are currently considered to be the most difficult to treat.
HCV and HIV are the two most prevalent blood-borne infections in the United States. Of the nearly one million people estimated to have HIV in the U.S., approximately 300,000 are believed to be co-infected with HCV. It can take 10 to 20 years following infection with hepatitis for a person to progress to end stage liver disease. However, in patients with HIV, the disease progresses far more quickly. With advances in HIV therapy prolonging the life expectancy of HIV patients, hepatitis C is now a major threat to people with HIV.
"The results of this study are groundbreaking news for the hundreds of thousands of Americans who are living with both hepatitis C and HIV," said Dr. Douglas Dieterich, Professor of Medicine, Mount Sinai School of Medicine, New York City and co-lead investigator of the APRICOT study. "These are patients who have fought long and hard to control their HIV -- for them to ultimately be defeated by a manageable disease like hepatitis C is unacceptable."
Results from the study report 40 percent overall efficacy among co- infected patients and, when analyzed by genotype, 62 percent efficacy in patients with genotypes 2 and 3, and 29 percent in those with genotype 1. Genotype 1 is typically the most difficult strain of HCV to treat. Four times more genotype 1 patients cleared the hepatitis C virus with Pegasys in combination with Copegus than with those treated with standard interferon/ribavirin combination therapy (29% vs. 7% respectively). Additionally, Pegasys monotherapy showed superior efficacy to treatment with standard interferon and ribavirin (20 percent vs. 12 percent), which is important for patients who cannot tolerate ribavirin.
The randomized, partially blinded international trial had a total of 868 HCV/HIV co-infected patients in 19 countries, and is currently the largest study conducted among this patient population. All patients were HCV positive, had compensated liver disease, a CD4+ count greater than 100 cells/mL, and stable HIV disease, with or without antiretroviral therapy. Patients were randomized to 48 weeks of treatment with interferon three times a week plus 800 mg/day of ribavirin, 180 mcg of Pegasys once weekly plus placebo, or 180 mcg of Pegasys once weekly with 800 mg/day of Copegus. Sustained virological response (SVR) was accessed at the end of 24 weeks of treatment-free follow up (week 72).
Negative predictability ranged from 98 to 100 percent at 12 weeks. Negative predictability means that patients can determine by week 12 if they are unlikely to respond to therapy with Pegasys so decisions about the continuance of treatment can be made in that time. In addition, HIV viral levels were not negatively impacted by treatment with Pegasys and Copegus combination therapy, and no new safety concerns were reported with this study. Pegasys is a well-tolerated medication, even with the addition of full doses of ribavirin. In this study, the most commonly reported side effects were fatigue, fever and headache.
The hepatitis C virus (HCV) is an RNA virus classified in the Flaviviridae family of viruses. Before the characterization of the virus, a diagnosis was largely one of exclusion (i.e. non-A, non-B hepatitis).
Data from the Third National Health and Nutrition Survey (1988-1994) estimate that there are approximately 3.9 million non-institutionalized, civilian Americans who have been infected with HCV. Of these, 2.7 million have chronic infection, indicating that HCV infection is the most common chronic blood-borne infection in the United States.
The estimated prevalence of infection varies greatly among different geographic locations and selected populations in the United States according to the varying prevalence of risk factors for infection. The study is published in this week's New England Journal of Medicine