Francesca Torriani, MD, and an international team of colleagues presented data from Roche’s APRICOT, or AIDS Pegasys Ribavirin International Coinfection Trial. The largest study of its kind, APRICOT included 860 HIV/HCV-coinfected participants in 19 countries who were receiving HCV treatment for the first time.
Participants were randomly assigned to one of three arms: 3 million IU standard interferon-alfa-2a three times weekly plus 800 mcg ribavirin daily (285 patients); 180 mcg pegylated interferon-alfa-2a (Pegasys, manufactured by Roche) once weekly plus placebo (286 patients); or the same doses of pegylated interferon plus ribavirin (289 patients), all for 48 weeks.
Baseline characteristics were similar in the three arms. About 81% were male, about 79% were white, about 10% were black, and the mean age was about 40 years. About 60% had genotype 1 HCV, 5% had genotype 2, 27% had genotype 3, and 7% had genotype 4. Participants had detectable baseline HCV RNA and elevated serum ALT. The mean total histological activity index (HAI) score was about 8.0, and about 16% had bridging fibrosis or cirrhosis. Subjects had stable HIV disease, with a mean CD4 cell count of about 530 cells/mm3; about 85% were on antiretroviral therapy and 60% had an HIV viral load below 50 copies/ml.
In an intent-to-treat analysis, 40% of patients treated with pegylated interferon/ribavirin achieved sustained virological responses (SVR), defined as undetectable HCV RNA at the end of a 24-week post-treatment follow-up period, compared with 20% of those receiving pegylated interferon monotherapy, and 12% of those receiving standard interferon/ribavirin (p < 0.001). Among patients with genotype 2 or 3, the corresponding SVR rates were 62%, 36%, and 20%, while in genotype 1 patients SVR was seen in 29%, 14%, and 7%, respectively. (For patients with HCV alone, SVR rates using pegylated interferon/ribavirin are about 80% for genotype 2 or 3 and about 45% for genotype 1).
Among patients with genotype 1, those with a baseline HCV RNA level greater than 800,000 IU/ml were significantly less likely to respond to any regimen than those with lower HCV viral loads (p < 0.001), but this difference was not seen in genotype 2 or 3 patients. Only two patients who failed to achieve an early virological response (at least a 2 log10 reduction in HCV RNA by week 12) went on to achieve SVR (a negative predictive value of 98-100%).
HCV therapy had no detrimental impact on HIV disease progression; in fact, HIV viral load decreased by about 0.7 log10 copies in patients treated with pegylated interferon. Absolute CD4 cell counts decreased in all three arms (interferon reduces white blood cell levels overall), but CD4 percentages remained stable. HCV treatment success rates did not vary by baseline CD4 cell count or use of antiretroviral therapy.
In terms of safety and tolerability, 39% of subjects in the standard interferon/ribavirin arm, 31% in the pegylated interferon monotherapy group, and 25% in the pegylated interferon/ribavirin arm discontinued treatment for any reason (p < 0.001). The rates of serious adverse events judged to be treatment-related were 5%, 10%, and 8%, respectively. Neutropenia and thrombocytopenia were more common in the arms that included pegylated interferon. The rate of mitochondrial toxicity -- a concern when ribavirin is combined with certain nucleoside reverse transcriptase inhibitors – was low in all arms.
“[Our] results demonstrate that the current regimen used for the treatment of chronic hepatitis C alone can also be applied to patients coinfected with HIV and HCV,” the researchers concluded. “Peginterferon alfa-2a plus ribavirin has a favorable risk-to-benefit ratio when used to treat such patients, a substantial proportion of whom are likely to benefit from therapy with this combination.” They recommended that coinfected patients with genotypes 2 or 3 should be treated for 48 weeks, even though 24 weeks is sufficient for genotype 2 or 3 patients with HCV alone.