Activation of CD8 T cells predicts progression of HIV infection in women coinfected with hepatitis C virus

J Infect Dis. 2010 Mar 15;201(6):823-34. doi: 10.1086/650997.

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 <26%) of CD8(+)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 >60% 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.

Publication types

  • Multicenter Study

MeSH terms

  • Acquired Immunodeficiency Syndrome / blood
  • Acquired Immunodeficiency Syndrome / complications*
  • Acquired Immunodeficiency Syndrome / immunology*
  • Adolescent
  • Adult
  • CD4 Lymphocyte Count
  • CD8-Positive T-Lymphocytes / immunology*
  • Disease Progression
  • Female
  • HIV / genetics
  • HIV / immunology
  • HIV Infections / blood
  • HIV Infections / complications
  • HIV Infections / immunology
  • Hepacivirus / genetics
  • Hepacivirus / immunology
  • Hepatitis C / blood
  • Hepatitis C / complications*
  • Hepatitis C / immunology*
  • Humans
  • Lymphocyte Activation*
  • Middle Aged
  • Proportional Hazards Models
  • RNA, Viral / blood
  • Risk Factors
  • United States / epidemiology
  • Women's Health
  • Young Adult

Substances

  • RNA, Viral