August 17, 2010

HCV/HIV Patients Who Fail IFN/ribavirin Can Still Use Protease Inhibitors

NEW YORK (Reuters Health) Aug 13 - In patients being simultaneously treated for HIV and hepatitis C virus (HCV), treating the HCV with interferon and ribavirin doesn't change its protease gene diversity nor make it resistant to protease inhibitors (PI), a new study has shown.
In other words, it looks as if "prior HCV treatment with interferon-ribavirin would not markedly impact the potential efficacy of subsequent HCV protease inhibitors treatment in coinfected patients," the researchers report in an August 3rd online article in the Journal of Infectious Diseases.

A majority of the patients in the study had not responded to interferon-ribavirin, but neither did they develop PI resistance mutations in the crucial HCV non structural protein gene 3 (NS3). This gene codes for an HCV protease with an important role in viral replication, the researchers explain.

The rapid multiplication of HCV RNA polymerase results in many circulating variants of the virus called quasispecies, some of which may carry resistant mutations, lead researcher Dr. Aarthi Chary from the Veterans Affairs Palo Alto Health Care System, California and colleagues write.

As a part of a wider prospective analysis of interferon-ribavirin treatment of HCV, the researchers evaluated the variations in HCV NS3 genes in 26 coinfected patients. All were receiving antiretroviral therapy (ART) for HIV, along with weekly or fortnightly subcutaneous interferon and daily oral ribavirin for HCV.

Eleven patients achieved a sustained viral response to interferon/ribavirin.

Baseline diversity in the NS3 gene prior to starting treatment, measured as the median inter nucleotide distance, was significantly greater in the patients who did not respond or who relapsed, the report says.

However, interferon-ribavirin treatment did not induce any new changes in the gene diversity or HCV protease inhibitor resistant mutations.

Although the study size was small, these results substantiate the potential role of HCV-protease inhibitors in difficult-to-treat HCV infections, the researchers write.

"As HCV protease inhibitors are introduced in clinical practice, further understanding of HCV NS3 diversity in this therapeutically challenging coinfected population is needed," Dr. Chary's team concludes.

J Infect Dis. Posted online August 3, 2010. Abstract


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