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Background:  Epidemiologic studies have yielded conflicting results regarding the role of chronic viral co-infections on HIV disease progression. Since T-cell activation is strongly associated with HIV disease progression and may be influenced by co-infections, we assessed the effect of 2 common chronic viral co-infections—human herpesvirus 8 (HHV-8) and hepatitis C virus (HCV)—on T-cell activation in vivo.

Methods:  HAART-treated and untreated HIV-infected patients were sampled from the University of California, San Francisco, Study of the Consequences of the Protease Inhibitor Era (SCOPE). HCV and HHV-8 co-infection were assessed by serum antibody testing. The percentages of activated (CD38⁺/DR⁺) CD4⁺ and CD8⁺ T cells were measured by flow cytometry and log-transformed to meet linear regression model assumptions.

Results:  Of the 233 patients evaluated, 187 were receiving HAART and 46 were untreated. Median values were:  age, 44 years; current CD4 count, 357 cells/mm³; current plasma HIV RNA level, 2.4 log₁₀ copies/mL. Of these patients, 58% had a positive HHV-8 serology and 30% had a positive HCV serology. The median percentages of activated CD4⁺ and CD8⁺ T cells were 6% and 19%, respectively. After adjustment for HAART use, plasma HIV RNA level, current CD4 count, and HHV-8 serostatus, a positive HCV serology was associated with a mean 1.3% increase in the percentage of activated CD4⁺ T cells (p = 0.008) and a mean 6% increase in the percentage of activated CD8⁺ T cells (p < 0.001). Conversely, after adjustment for these factors, a positive HHV-8 serology was only associated with a mean increase of 0.8% activated CD4⁺ T cells ( = 0.07), and no evidence for a difference in the percentage of activated CD8⁺ T cells (p = 0.85).

Conclusions:  Among HIV-infected patients, HCV co-infection is associated with significant increases in both CD4⁺ and CD8⁺ T-cell activation while HHV-8 co-infection may be associated with only a modest increase in CD4⁺ but not CD8⁺ T cell activation. This discrepancy may be the result of the higher levels of sustained viral replication observed in HCV infection as compared to HHV-8 infection.

Keywords: T cell activation; human herpesvirus 8; hepatitis C virus