Activation of CD8 T Cells Predicts Progression of HIV Infection in Women Coinfected with Hepatitis C Virus

Abstract

Background. Because activation of T cells is associated with human immunodeficiency virus (HIV) pathogenesis, CD4 and CD8 activation levels in patients coinfected with HIV and hepatitis C virus (HCV) may explain conflicting reports regarding effects of HCV on HIV disease progression. Methods. Kaplan-Meier and multivariate Cox regression models were used to study the risk of incident clinical AIDS and AIDS-related deaths among 813 HCV-negative women with HIV infection, 87 HCV-positive nonviremic women with HIV coinfection, and 407 HCV-positive viremic women with HIV coinfection (median follow-up time, 5.2 years). For 592 women, the percentages of activated CD4 and CD8 T cells expressing HLA-DR (DR) and/or CD38 were evaluated. Results. HCV-positive viremic women had a statistically significantly higher percentage of activated CD8 T cells (P<.001) and a statistically significantly higher incidence of AIDS compared with HCV-negative women (P<.001 [log-rank test]). The AIDS risk was greater among HCV-positive viremic women in the highest tertile compared with the lowest tertile (>43% vs +CD38⁺DR⁺ T cells (hazard ratio, 2.94 [95% confidence interval, 1.50–5.77]; P=.001). This difference was not observed in the HCV-negative women (hazard ratio, 1.87 [95% confidence interval, 0.80–4.35]; P=.16). In contrast, CD4 activation predicted AIDS in both groups similarly. Increased percentages of CD8⁺CD38⁻DR⁺, CD4⁺CD38⁻DR⁻, and CD8⁺CD38⁻DR⁻ T cells were associated with a 160% decreased risk of AIDS for HCV-positive viremic women and HCV-negative women. Conclusion. HCV-positive viremic women with HIV coinfection who have high levels of T cell activation may have increased risk of AIDS. Earlier treatment of HIV and HCV infection may be beneficial.