Effect of HCV Genotype on Hepatitis C and HIV Disease Progression

HIV-1 and hepatitis C virus (HCV) coinfection is common in various at-risk groups. Moreover, coinfected individuals have lower rates of HCV clearance, and several studies have shown that HCV RNA levels are higher and that CD4⁺ T cell counts may be lower in coinfected individuals.

There is also growing evidence that HCV-related hepatic disease progression is accelerated in the setting of HIV-1 coinfection. Although several studies have suggested that HCV infection may adversely influence the clinical progression of HIV-1 disease, other studies have not.

These conflicting studies differ in the populations studied, the extent of potent antiretroviral therapy use, the ability to adjust for immunologic and virologic parameters, and the duration of follow-up. In addition, it has been demonstrated that, in cohorts of coinfected individuals who were followed up long term, HCV RNA levels independently predict the clinical progression of HIV-1 disease.

The relationship between HCV genotype and HIV-1 and HCV infection has also been explored. Although HCV genotype is unequivocally an important predictor of response to anti-HCV treatment, there have been suggestions that it might also influence HCV RNA levels and even the natural history of HCV and HIV-1 disease.

In the present study, American and Chinese researchers assess the relationship between HCV genotype and (1) HCV RNA levels in HIV-1uninfected participants with hemophilia and (2) CD4⁺ T cell counts, HIV-1 RNA levels, HCV RNA levels, and clinical progression of HIV-1 disease in HIV-1/HCVcoinfected participants with hemophilia.

Results

The present study analyzed data from a cohort of 207 HIV-1infected and 126 HIV-1uninfected children and adolescents with hemophilia who enrolled in the Hemophilia Growth and Development Study and were followed for 7 years.

The mean HCV RNA level was higher in the participants in the HCV genotype 1 group than in the participants the HCV nongenotype 1 group, among both the HIV-1infected (difference, +0.33 log₁₀ copies/mL; P = .038) and HIV-1uninfected (difference, +0.59 log₁₀ copies/mL; P = .008) participants.

Conclusions

In conclusion, the authors write, “The present study has demonstrated that HCV genotype has an effect on HCV replication in both individuals infected with HCV only and individuals coinfected with HIV-1 and HCV.

“In addition, the present study has shown that HCV infection may adversely influence the natural history of HIV-1 disease in HIV-1/HCVcoinfected individuals.

“Additional studies are needed to further define the virologic and/or immunologic mechanisms behind these observations, because such mechanisms may provide valuable insight into how to prioritize the timing of HCV treatment in HIV-1/HCVcoinfected individuals and into HIV-1 and HCV immunopathogenesis.

“The observation in the present study that both the absolute CD4⁺ T cell count and the percentage of CD4⁺ T cells were significantly decreased in the participants in the HCV genotype 1 group is a novel finding that will need to be confirmed in other cohorts.”

Editorial commentary on this article by Nunez and Soriano, also in The Journal of Infectious Diseases.

12/08/04