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.
Kovacs
Andrea
A
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
Karim
Roksana
R
Mack
Wendy J
WJ
Xu
Jiaao
J
Chen
Zhi
Z
Operskalski
Eva
E
Frederick
Toni
T
Landay
Alan
A
Voris
John
J
Spencer
La Shonda
LS
Young
Mary A
MA
Tien
Phyllis C
PC
Augenbraun
Michael
M
Strickler
Howard D
HD
Al-Harthi
Lena
L
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