ICAAC: Pegylated interferon-alpha 2a produces good results in HIV / HCV patients with genotype 1

An anti-hepatitis C treatment regimen consisting of pegylated interferon-alpha 2a (Pegasys) plus ribavirin (Copegus / Rebetol / Virazole) provides a high rate of virological response in HIV-positive patients coinfected with hepatitis C virus through to week 24 of treatment, according to interim Spanish research presented to the 44^th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in Washington. In particular, the investigators emphasise that a good virological response was seen at weeks 12 and 24 in patients infected with hepatitis C genotype 1, the hardest of all the hepatitis C genotypes to treat.

Investigators from the ongoing non-randomised PRESCO study presented interim four, twelve and 24 week data for patients recruited to a multi-centre study into the safety and efficacy of pegylated interferon and ribavrin for the treatment of hepatitis C in HIV-positive patients. Data were presented on the 138 patients who had completed four weeks follow-up, the 147 individuals who had completed twelve weeks of the trial, and the 120 patients who had contributed 24 weeks of data.

Eligibility criteria for the PRESCO study include a CD4 cell count above 300 cells/mm³ and high liver enzymes. Exclusion criteria include psychiatric illness, alcohol abuse, ddI (didanosine, Videx / VidexEC) use, and cirrhosis.

Individuals were treated with hepatitis C therapy consisting of pegylated interferon-alpha 2a at a dose of 180µg per week, plus ribavirin at a dose of 1000 to 1200mg per day. Individuals who were infected with hepatitis C genotypes 1 and 4 (the hardest to treat) received twelve months of treatment, and individuals with genotypes 2 and three received six months of hepatitis C therapy.

Overall, 62% of patients had achieved a 2 log₁₀ reduction in hepatitis C viral load after four weeks of treatment. The best results were seen in patients infected with hepatitis C genotypes 2 or 3, with 86% achieving a 2 log₁₀ fall in hepatitis C viral load. Of the patients infected with genotype 4, 53% achieved this fall in hepatitis C viral load, as did 45% of individuals infected with hepatitis C genotype 1, the hardest to treat of all the genotypes and the most prevalent in the United Kingdom.

After twelve weeks of hepatitis C therapy, a total of 86% of patients had experienced a 2 log₁₀ or greater fall in their hepatitis C viral load. As expected, the best results were seen in patients infected with genotypes 2 or 3 (97% achieving a 2 log₁₀ reduction). There were also encouraging results for patients infected with genotypes 1 and 4, with 80% of patients infected with genotype 1 experiencing a 2 log₁₀ or greater fall in hepatitis C viral load, and 70% of individuals with genotype 4 experiencing a similar result.

In their 24 week analysis, the investigators established how many individuals had achieved a virological response to hepatitis C treatment (defined as a hepatitis C viral load below 60 IU/ml).

Intent-to-treat analysis showed that, at week 24, overall 66% of patients had achieved a virological response, including 63% of patients infected with hepatitis C genotype 1. On-treatment analysis showed that overall 86% of patients had a virologic response, including 88% of patients infected with genotype 1.

There were a total of 13 (11%) virologic failures, including six patients infected with genotype 1 and four individuals with genotype 4. There was, however, a high rate of treatment discontinuation due to adverse events (18 patients) and other causes (ten patients), 23% of patients withdrawing from the study before completing 24 weeks of treatment.

Dose reductions in pegylated interferon were required in 35 patients, and 41 individuals reduced their dose of ribavirin.

The investigators note that the four and twelve-week results are as good as those seen in hepatitis C virus (HCV) monoinfected patients. They conclude, “24 week data from the PRESCO trial show that pegylated interferon-alpha 2a provides high rates of virological response in HCV/HIV-positive patients, even in those carrying hepatitis C virus genotype 1.”

They speculate that higher doses of ribavirin may have contributed to these good results, and concede that there was a high rate of withdrawal from the study because of side-effects.