Coinfection

HIV/HCV Coinfected Have Stronger CD8 T-cell Response to HCV

HIV positive people coinfected with hepatitis C virus (HCV) demonstrated stronger CD8 T-cell responses against HCV, which may contribute to accelerated liver disease progression.

An estimated one-third of HIV positive people also have HCV, which is transmitted in similar ways. HIV/HCV coinfected individuals experience more rapid liver fibrosis progression on average, may be more likely to develop liver cirrhosis or cancer, and tend to respond less well to interferon-based hepatitis C treatment.

A study reported in the March 2011 Journal of Viral Hepatitis shed further light on the biological mechanisms underlying different outcomes in HIV/HCV coinfected and HCV monoinfected patients.

Lisa Barrett from Memorial University of Newfoundland and colleagues evaluated the role of the immune system in accelerated liver disease progression in coinfected people.

In general, liver disease develops over years in people with HIV/HCV coinfection, compared to decades with HCV monoinfection, the study authors noted as background. Fibrosis is not caused directly by the virus, however, but rather is an outcome of the immune response against it, which includes inflammation and activation of cell-repair mechanisms.

Some investigators, including Daniel Fierer and colleagues at Mt. Sinai Medical Center in New York City, have described very rapid fibrosis progression in a cohort of men who were already HIV positive when they subsequently acquired HCV, presumably through sex.

In the present analysis, the researchers compared the frequency, magnitude, breadth, and specificity of peripheral blood CD4 and CD8 T-cell responses between HIV positive and HIV negative hepatitis C patients. They also looked at differences between coinfected people with various HCV antibody and HCV RNA viral load status.

Results

• In general, HIV/HCV coinfection tended to reduce the frequency and breadth of anti-HCV CD8 T-cell responses.
• However, CD8 T-cell responses that were present were substantially stronger in coinfected compared with HCV monoinfected individuals.
• In all groups, HCV-specific CD4 T-cell responses were rare and weak, regardless of either current or nadir (lowest-ever) CD4 counts in HIV positive individuals.
• HIV/HCV coinfected people without anti-HCV antibodies demonstrated restricted breadth of HCV-specific CD8 T-cell responses and lower B-cell counts.

Based on these findings, the study authors concluded, "The greatest difference between HIV/HCV coinfected and HCV monoinfected groups was substantially stronger HCV-specific CD8+ T-cell responses in the HIV[/HCV] coinfected group, which may relate to accelerated liver disease in this setting."

Investigator affiliations: Immunology Program, Division of BioMedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, NL, Canada; Department of Internal Medicine, Dalhousie University, Halifax, NS, Canada; HIV Program, Eastern Health District, St. John's, NL, Canada; Hepatitis C Program, Division of Gastroenterology, Capital Health District, Halifax, NS, Canada.

5/6/11

Reference
L Barrett, M Gallant, C Howley, et al. Stronger hepatitis C virus-specific CD8(+) T-cell responses in HIV coinfection. Journal of Viral Hepatitis 18(3):170-180 (abstract). March 2011.