T Cell Activation and Senescence Predict Subclinical Carotid Artery Disease in HIV-Infected Women

Department of Epidemiology and Population Health, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York 10461, USA.
The Journal of Infectious Diseases (Impact Factor: 6). 02/2011; 203(4):452-63. DOI: 10.1093/infdis/jiq071
Source: PubMed


Individuals infected with human immunodeficiency virus (HIV) have increased risk of cardiovascular events. It is unknown whether T cell activation and senescence, 2 immunologic sequelae of HIV infection, are associated with vascular disease among HIV-infected adults.
T cell phenotyping and carotid ultrasound were assessed among 115 HIV-infected women and 43 age- and race/ethnicity-matched HIV-uninfected controls participating in the Women's Interagency HIV Study. Multivariate analyses were used to assess the association of T cell activation (CD38(+)HLA-DR(+)) and senescence (CD28(-)CD57(+)) with subclinical carotid artery disease.
Compared with HIV-uninfected women, frequencies of CD4(+)CD38(+)HLA-DR(+), CD8(+)CD38(+)HLA-DR(+), and CD8(+)CD28(-)CD57(+) T cells were higher among HIV-infected women, including those who achieved viral suppression while receiving antiretroviral treatment. Among HIV-infected women, adjusted for age, antiretroviral medications, and viral load, higher frequencies of activated CD4(+) and CD8(+) T cells and immunosenescent CD8(+) T cells were associated with increased prevalence of carotid artery lesions (prevalence ratio(lesions) associated with activated CD4(+) T cells, 1.6 per SD [95% confidence interval {CI}, 1.1-2.2]; P = .02; prevalence ratio(lesions) associated with activated CD8(+) T cells, 2.0 per SD [95% CI, 1.2-3.3]; P < .01; prevalence ratio(lesions) associated with senescent CD8(+) T cells, 1.9 per SD [95% CI, 1.1-3.1]; P = .01).
HIV-associated T cell changes are associated with subclinical carotid artery abnormalities, which may be observed even among those patients achieving viral suppression with effective antiretroviral therapy.

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    • "Despite the successful HIV therapy noted in the GRACE substudy, there seemed to be a higher frequency of the CD8+ CD28− phenotype. This possible treatment-resistant expansion and persistence of cells with a senescence phenotype may have potential for long-term cardiovascular [44], metabolic, and other aging-associated consequences. "
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    • "Persistent immune activation is a critical component of HIV pathogenesis (reviewed in [3]). Although T cell activation is reduced in successfully treated HIV-infected individuals, it remains increased relative to HIV uninfected control groups [9]; [10], and this is thought to contribute to increased morbidity and premature aging among those successfully treated with cART [10]; [12]; [44]. Understanding factors that modulate T cell activation may identify novel approaches to alter HIV disease progression. "
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    • "These findings suggest that HIV infection itself may increase the risk for cardiovascular disease, as it has been shown for other chronic inflammatory diseases [9] in the non-HIV setting. Many markers of inflammation are markedly elevated in individuals with untreated HIV infection and are only partially reversed by effective combination antiretroviral therapy [31]. "
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