Retreatment with Pegylated Interferon alfa-2a (Pegasys) plus Weight-based Ribavirin in HIV-HCV Coinfected Non-responders and Relapsers to Prior Hepatitis C Treatment: The PILOT-NR Study

By Liz Highleyman

Despite improvements in hepatitis C therapy, about half of patients with chronic hepatitis C do not achieve sustained virological response (SVR) on their first treatment attempt, especially if they have factors that predict poor response, including HCV genotype 1, African race/ethnicity, or HIV coinfection.

However, some people can achieve sustained response when retreated with pegylated interferon plus ribavirin, especially if they received suboptimal therapy the first time around. Suboptimal therapy may include, for example, use of conventional rather than pegylated interferon, conventional or pegylated interferon monotherapy, interferon with an insufficient dose of ribavirin, or inadequate treatment duration.

In a study presented at the recent 58th Annual Meeting of the American Association for the Study of Liver Diseases in Boston (November 2-6, 2007), researchers from Hospital Carlos III in Madrid, Spain, conducted a prospective study in which 51 HIV-HCV coinfected prior non-responders or relapsers to suboptimal interferon-based therapy were retreated with 180 mcg/week pegylated interferon alfa-2a (Pegasys) plus weight-adjusted ribavirin (1000 mg/day if <75 kg; 1200 mg/day if >75 kg) for 48 weeks.

Most participants (80%) were men and the mean age was 42 years. They had well-controlled HIV disease, with a mean CD4 count of 696 cells/mm³, 89% with undetectable HIV RNA (mean 6.1 log IU/mL), and 90% on HAART. Nearly three-quarters (72%) had HCV genotypes 1 or 4, and 59% had advanced liver fibrosis, defined as >9.5 kPa using FibroScan transient elastometry.

Prior suboptimal regimens used were interferon monotherapy (23%), conventional interferon plus ribavirin (27%), and pegylated interferon plus 800 mg/day ribavirin (50%); 800 mg/day is now generally considered a suboptimal dose. The mean length of these treatments was 6.6 months. Overall, 64% of patients were prior non-responders and 36% were prior relapsers.

Results

·         Retreatment with pegylated interferon plus weight-based ribavirin produced SVR in 39% of patients (27% for genotype 1/4 and 70% for genotype 2/3; P=0.02 ).

·         The SVR rate was slightly lower in prior non-responders compared with prior relapsers (30 vs 58%), but the difference was non-significant.

·         The SVR rate was also lower for patients with advanced liver fibrosis versus those milder liver disease (18 vs 60%; P=0.02).

·         Ribavirin plasma trough levels at week 4 were comparable between patients who achieved SVR and those who did not (2.53 vs 2.13 mcg/mL).

·         In a multivariate analysis, factors that independently predicted SVR were:

o        Lack of advanced liver fibrosis (odds ratio [OR] 50; 95% CI 2.12-100; P=0.02);

o        Lower baseline HCV RNA (OR 16; 95% CI 1.5-166; P<0.05);

o        HCV genotype 2 or 3 (OR 33.3; 95% CI 1.03-166; P<0.05).

Conclusion

“Re-treatment with pegylated interferon alfa-2a plus weight-adjusted ribavirin for 12 months allows HCV clearance in a significant proportion of HIV-HCV [coinfected] patients,” the researchers concluded. “The better chances of HCV eradication were seen in patients with mild liver fibrosis, low HCV RNA, and genotype 2-3.”

11/20/07

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