Pegylated interferon in HIV/HCV co-infection

The first data on the use of pegylated interferon alpha 2a and ribavirin combination therapy for hepatitis C infection in people with HIV were presented today at the Ninth Annual Retroviruses Conference in Seattle.

The study compared pegylated interferon alpha-2a and ribavirin with interferon alpha-2a in HIV -positive individuals on stable HAART or treatment-naive individuals with CD4 cell counts above 350/mm. The results presented today covered the first 24 weeks of the study, and represented a interim analysis designed to check if the new forumulation of interferon alpha is safe for use in co-infected people.

The study randomised 133 individuals; after 24 weeks, 33% of those with HCV genotype 1 had HCV viral load below 60 IU by the Roche Amplicor assay in the pegylated interferon group, compared with 7% of the alpha interferon group, while in those with genotype 2 or 3, 80% of the pegylated interferon group and 40% of the alpha interferon group had undetectable HCV viral load.

Participants in this study were mandated to have a liver biopsy if they did not have HCV RNA below 60 IU at week 24. Of the virological non-responders, 40% of the pegylated interferon group and 26% of the alpha interferon group showed histological improvement, a measure of reduction in liver inflammation and damage (a non-significant difference).

There was no difference in premature discontinuation due to adverse events, although grade 4 leukopenia and elevated liver enzyme levels were more common in the pegylated interferon group. Grade 4 events (severe adverse events) occurred in 15% of the pegylated interferon group compared to 12% of the interferon alpha group, a statistically significant difference. Lead investigator Ray Chung attributed the low discontinuation rate in part to the study's practice of dose escalating the ribavirin treatment from 600mg to 1,000mg during the first eight weeks of the study. Only one grade 4 case of depression was reported in this study, in the pegylated interferon group.

A fibrosis score of 0 to 2 was found to be associated with a better response to therapy, indicating the importance for success of this treatment of early identification of HCV infection. People with more advanced liver disease were significantlly less likely to have experienced a virological response by week 24, although it should be noted that this is a 48 week study and that interferon alpha-2a and ribavirin combination therapy, the current standard of care, is administered over 48 weeks.

No significant effect on HIV viral load was seen during the study in either arm, and CD4 cell percentage increased in both arms during the study, an indicator of immune system improvement.