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


CONCLUSIONS
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.
Maternal, Child, and Adolescent, Center for Infectious Diseases and Virology, University of Southern California, Keck School of Medicine, HRA 300, 1640 Marengo St, Los Angeles, CA 90033, USA. akovacs@usc.edu
Andrea
A
Kovacs
Roksana
R
Karim
Wendy J
WJ
Mack
Jiaao
J
Xu
Zhi
Z
Chen
Eva
E
Operskalski
Toni
T
Frederick
Alan
A
Landay
John
J
Voris
La Shonda
LS
Spencer
Mary A
MA
Young
Phyllis C
PC
Tien
Michael
M
Augenbraun
Howard D
HD
Strickler
Lena
L
Al-Harthi
D000163:Acquired Immunodeficiency Syndrome / Q000097:blood / Q000150:complications* / Q000276:immunology*; D000293:Adolescent; D000328:Adult; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018450:Disease Progression; D005260:Female; D006678:HIV / Q000235:genetics / Q000276:immunology; D015658:HIV Infections / Q000097:blood / Q000150:complications / Q000276:immunology; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology; D006526:Hepatitis C / Q000097:blood / Q000150:complications* / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D008875:Middle Aged; D016016:Proportional Hazards Models; D012367:RNA, Viral / Q000097:blood; D012307:Risk Factors; D014481:United States / Q000453:epidemiology; D016387:Women's Health; D055815:Young Adult
D012367:RNA, Viral