HCV protease inhibitors likely to work for co-infected patients previously treated for HCV

Michael Carter
Published: 30 August 2010

Previous treatment with pegylated interferon and ribavirin will not reduce the effectiveness of hepatitis C protease inhibitors in HIV-positive patients, US investigators report in the September 15th edition of the Journal of Infectious Diseases.

The study involved 26 HIV/hepatitis-co-infected patients. The genetic diversity of hepatitis C was evaluated in patients before and after they started treatment for this infection with pegylated interferon and ribavirin. This analysis showed that it was similar in patients who achieved a sustained virologic response to such treatment and those who did not.

“These results suggest that prior HCV [hepatitis C virus] treatment with interferon-ribavirin would not markedly impact the potential efficacy of subsequent HCV PI [protease inhibitor] treatment in coinfected patients”, comment the investigators.

Liver disease caused for hepatitis C is now an important cause of death in HIV-positive patients who are co-infected with this virus. 

Hepatitis C can be treated. The current standard of care is pegylated interferon combined with ribavirin. The goal of treatment is a cure (or sustained virologic response), defined as an undetectable hepatitis C viral 24 weeks after the completion of therapy.

However, only a minority of HIV-positive patients who are chronically infected with hepatitis C clear the infection with this treatment.

It is hoped that more effective anti-hepatitis C drugs will soon become available, and the protease inhibitors boceprevir and telaprevir have shown good results in clinical trials involving both treatment-naïve and treatment experienced hepatitis C monoinfected patients.

Anti-hepatitis C protease inhibitors target a crucial step in the replication of the virus called the N-terminal domain of nonstructural protein 3 (NS3). High levels of genetic diversity at the amino acid and nucleotide levels have been observed in NS3.  It is possible that previous therapy for hepatitis C could increase diversity within this gene, thereby reducing the effectiveness of protease inhibitors.

To see if this is the case investigators evaluated the impact of interferon-ribavirin therapy on the genetic diversity of the hepatitis C NS3 protease gene sequence in HIV-positive patients who were receiving antiretroviral therapy.

A total of 26 patients were enrolled in the study. All but one was male, the mean age was 45 years, 46% were African American and 42% were white.

The genetic diversity of hepatitis C was evaluated before therapy for hepatitis C was started and again no more than four weeks after the completion of this treatment.

Treatment cleared (an undetectable hepatitis C viral load six months after the completion of therapy) hepatitis C infection in eleven patients.

There was no evidence that response to pegylated interferon-ribavirin therapy would affect susceptibility to protease inhibitors.

At both the nucleotide and amino acid levels, there was no significant change between baseline and the completion of therapy in the NS3 gene in those who responded to therapy or in those patients who did not.

However, there was evidence that the genetic diversity of the NS3 gene at baseline had an impact on the efficacy of pegylated interferon and ribavirin therapy. Those who did not clear the virus had significantly greater diversity at the nucleotide (p = 0.004) and amino acid (p = 0.009) levels than patients who had a successful response to such therapy.

“NS3 resistance mutations are occasionally found in PI treatment-naïve patients; however, interferon-ribavirin treatment does not appear to select for these mutations or increase their prevalence”, comment the investigators.

They conclude, “our results indicate that the potential efficacy of HCV PIs will be unaffected by previous HCV treatment in coinfected patients.”

Reference

 

Charv A et al. Impact of interferon-ribavirin treatment on hepatitis C virus (HCV) protease quasispecies diversity in HIV- and HCV-coinfected patients. J Infect Dis 202: 889-93, 2010.

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