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

Andrea Kovacs, Roksana Karim, Wendy J. Mack, Jiaao Xu, Zhi Chen, Eva Operskalski, Toni Frederick, Alan Landay, John Voris, La Shonda Spencer, Mary A. Young, Phyllis C. Tien, Michael Augenbraun, Howard Strickler, Lena Al-Harthi

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Abstract

Background. Because activation of T cells is associated with human immunodeficiency virus (HIV) patho-genesis, 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.

Original languageEnglish (US)
Pages (from-to)823-834
Number of pages12
JournalJournal of Infectious Diseases
Volume201
Issue number6
DOIs
StatePublished - 2010

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Virus Diseases
Hepacivirus
HIV
T-Lymphocytes
Acquired Immunodeficiency Syndrome
Coinfection
HLA-DR Antigens
Proportional Hazards Models
Disease Progression

ASJC Scopus subject areas

  • Infectious Diseases
  • Immunology and Allergy

Cite this

Kovacs, A., Karim, R., Mack, W. J., Xu, J., Chen, Z., Operskalski, E., ... Al-Harthi, L. (2010). Activation of CD8 T cells predicts progression of HIV infection in women coinfected with hepatitis C virus. Journal of Infectious Diseases, 201(6), 823-834. https://doi.org/10.1086/650997

Activation of CD8 T cells predicts progression of HIV infection in women coinfected with hepatitis C virus. / Kovacs, Andrea; Karim, Roksana; Mack, Wendy J.; Xu, Jiaao; Chen, Zhi; Operskalski, Eva; Frederick, Toni; Landay, Alan; Voris, John; Spencer, La Shonda; Young, Mary A.; Tien, Phyllis C.; Augenbraun, Michael; Strickler, Howard; Al-Harthi, Lena.

In: Journal of Infectious Diseases, Vol. 201, No. 6, 2010, p. 823-834.

Research output: Contribution to journalArticle

Kovacs, A, Karim, R, Mack, WJ, Xu, J, Chen, Z, Operskalski, E, Frederick, T, Landay, A, Voris, J, Spencer, LS, Young, MA, Tien, PC, Augenbraun, M, Strickler, H & Al-Harthi, L 2010, 'Activation of CD8 T cells predicts progression of HIV infection in women coinfected with hepatitis C virus', Journal of Infectious Diseases, vol. 201, no. 6, pp. 823-834. https://doi.org/10.1086/650997
Kovacs, Andrea ; Karim, Roksana ; Mack, Wendy J. ; Xu, Jiaao ; Chen, Zhi ; Operskalski, Eva ; Frederick, Toni ; Landay, Alan ; Voris, John ; Spencer, La Shonda ; Young, Mary A. ; Tien, Phyllis C. ; Augenbraun, Michael ; Strickler, Howard ; Al-Harthi, Lena. / Activation of CD8 T cells predicts progression of HIV infection in women coinfected with hepatitis C virus. In: Journal of Infectious Diseases. 2010 ; Vol. 201, No. 6. pp. 823-834.
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abstract = "Background. Because activation of T cells is associated with human immunodeficiency virus (HIV) patho-genesis, 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.",
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T1 - Activation of CD8 T cells predicts progression of HIV infection in women coinfected with hepatitis C virus

AU - Kovacs, Andrea

AU - Karim, Roksana

AU - Mack, Wendy J.

AU - Xu, Jiaao

AU - Chen, Zhi

AU - Operskalski, Eva

AU - Frederick, Toni

AU - Landay, Alan

AU - Voris, John

AU - Spencer, La Shonda

AU - Young, Mary A.

AU - Tien, Phyllis C.

AU - Augenbraun, Michael

AU - Strickler, Howard

AU - Al-Harthi, Lena

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N2 - Background. Because activation of T cells is associated with human immunodeficiency virus (HIV) patho-genesis, 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.

AB - Background. Because activation of T cells is associated with human immunodeficiency virus (HIV) patho-genesis, 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.

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