HCV treatment failure not due to change in HCV genotype in HIV-positive IDUs

Injecting drug users (IDUs) co-infected with hepatitis C virus (HCV) and HIV do not appear to fail HCV therapy due to a shift in the dominant strain of HCV, according to a study presented in the 1^st October edition of The Journal of Infectious Diseases. The study found that persistent co-infection with more than one strain or ‘genotype’ of HCV is rare, and that interferon-based treatment often fails in these patients for reasons other than the presence of hidden, resistant strains of HCV in the body.

The possibility that IDUs, particularly those co-infected with HIV, may be at an elevated risk of infection with more than one strain of HCV has been put forward by a number of experts over the past few years. This could be a cause of the low rates of HCV treatment success observed in HIV-co-infected IDUs with anti-HCV therapy.

Methods to test for the genotypes of HCV in blood samples could miss those that are present at low levels. Accordingly, investigators from Spain wished to find out whether any hidden HCV strains could be responsible for the high failure rate of HCV treatment in these patients. They hypothesised that effective clearance of interferon-susceptible strains could clear the way for resistant strains of HCV to replicate and become dominant in the body.

To test this theory, the researchers took blood samples from 203 former IDUs before and at least six months after a six-month course of interferon-based therapy. All of the patients had failed to clear HCV infection by six months after the end of treatment.

After testing the genotypes of HCV found in the samples, the researchers discovered that none of the patients showed a switch in the predominant HCV strain.

“Changes in HCV genotype were not found in any patient when samples obtained before and after HCV therapy were compared,” they conclude. “HCV therapy did not seem to select for interferon-resistant HCV genotypes that might have been present at baseline.”

However, the researchers stop short of suggesting alternative explanations for the low treatment response rate in HIV-co-infected IDUs.

Most of the patients in the study had hard-to-treat genotypes 1 or 4 (65 and 8%, respectively), with 2% having genotype 2 and 26% having genotype 3. Co-infection was detected in only three patients (1%) at the start of the study.

The patients were treated with a range of interferon-based therapies as a part of five separate clinical trials. These included therapy with conventional interferon alfa alone (25%), interferon with ribavirin (33%) and peginterferon alfa with ribavirin (42%). None of the patients were co-infected with hepatitis B, had CD4 cell counts below 200 cells/mm³ or had active drug or alcohol addiction.

The investigators suggest that the low frequency of co-infection may be a consequence of HCV’s biology. In contrast to HIV, HCV does not insert its genetic material into the nucleus of the human cells it infects, so there is no stored ‘reservoir’ of different HCV strains lying dormant within human cells.

This, they argue, means that people infected with more than one strain of HCV tend to clear the weaker strains of HCV as they are out-competed by stronger strains. In the absence of a hidden store of HCV strains, this eventually leads to these people only having one strain of HCV in the body.

“Co-infection with multiple HCV genotypes, even in IDUs and in the setting of HIV infection, should be considered to be a very rare event,” they conclude. “[It] does not explain the lower efficacy of HCV therapy in this population.”