Further data on pegylated interferon in HCV/HIV coinfection

Following the early results of a similar US study presented at the Retroviruses Conference in Seattle earlier this year, researchers from France today reported 48 week data from the RIBAVIC trial investigating the use of pegylated interferon plus ribavirin in people coinfected with hepatitis C virus (HCV) and HIV. Data were presented at a Late Breaker session at the Fourteenth International AIDS Conference in Barcelona.

RIBAVIC (ANRS HC02) compared the use of pegylated interferon and ribavirin with standard interferon and ribavirin in HIV-positive people who were naïve to HCV therapy, were HCV RNA positive, had had a liver biopsy within the last eighteen months, had stable HIV viral load (defined as less than a one log change within the last three months), were on either stable antiretroviral therapy or no therapy, and who had CD4 counts above 200 cells.

The primary endpoint was HCV viral load at 72 weeks. Results reported here are from an interim analysis completed at 48 weeks.

Of 432 screened patients, 416 were randomised to one of the two treatment arms. Pegylated interferon was dosed at 1.5micrograms/kg once a week; standard interferon at 3MIU/kg three times a week; and ribavirin at 12mg/kg per day.

Of 208 people randomised to the pegylated interferon arm, 148 have completed 48 weeks of treatment. The comparative figure for the 210 people randomised to standard interferon is 152. Around 35 people per arm discontinued therapy early.

Participants had been HIV-positive for a median of 10.6 years. Median CD4 was 515 cells. Sixty-seven per cent had HIV viral load below 400 copies, and 80% were on HAART.

Median duration of HCV infection was 13.3 years for the pegylated group and 14.6 years for standard interferon. Metavir scores (which reflect liver health) were 1.8 and 1.7 for inflammation, and 2.3 and 2.3 for fibrosis in the pegylated and standard therapy groups respectively. Thirty-nine per cent were staged at either F3 or F4 (F4 is cirrhosis). The hard-to-treat genotypes 1 and 4 were present in 69% of the pegylated group and 64% of the standard interferon group. ALT was raised 2.2 times the upper limit of normal in both arms.

After 48 weeks by intent to treat analysis, 37% (53 of 143) of the pegylated group were HCV PCR negative, compared to 24% (37 of 152) of the standard therapy group. By per protocol analysis (including only those patients who remained on treatment), these proportions were 51% (45 of 89) and 31% (32 of 103) respectively. In both analyses these differences were statistically significant.

Assessing the treatments by genotype, the researchers found no differences between arms for those with genotypes 2 and 3, with around 45% of participants in both arms obtaining a negative HCV PCR. This figure is lower than that observed in people with HCV monoinfection; typically 80%. However for genotypes 1 and 4, pegylated interferon was much the more effective treatment (26% versus 9%).

Though pegylated interferon is intended to reduce toxicity, the frequency of serious adverse events was similar across the treatment arms at around 21%. The most common events were psychiatric, sepsis and pneumonia.