학술논문

T-Cell Activation, Both Pre- and Post-HAART Levels, Correlates With Carotid Artery Stiffness Over 6.5 Years Among HIV-Infected Women in the WIHS
Document Type
article
Source
JAIDS Journal of Acquired Immune Deficiency Syndromes. 67(3)
Subject
Medical Microbiology
Biomedical and Clinical Sciences
Immunology
Atherosclerosis
Cardiovascular
Infectious Diseases
HIV/AIDS
Clinical Research
Aetiology
2.1 Biological and endogenous factors
Infection
Good Health and Well Being
ADP-ribosyl Cyclase 1
Adult
Antiretroviral Therapy
Highly Active
CD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
Carotid Artery Diseases
Female
HIV Infections
HIV Seronegativity
HLA-DR Antigens
Humans
Linear Models
Lymphocyte Activation
Middle Aged
Predictive Value of Tests
Prospective Studies
Vascular Stiffness
T-cell activation
arterial stiffness
HIV infection
Clinical Sciences
Public Health and Health Services
Virology
Clinical sciences
Epidemiology
Public health
Language
Abstract
ObjectiveT-cell activation is a major pathway driving HIV disease progression. Little is known regarding the impact of T-cell activation on HIV-associated atherosclerosis and cardiovascular disease, a common comorbidity in HIV infection. We hypothesized that T-cell activation will predict vascular stiffness, a measure of subclinical atherosclerosis.DesignLinear regression models evaluated the covariate-adjusted association of T-cell activation with vascular stiffness.MethodsCD38 and HLA-DR expression on CD4⁺ and CD8⁺ T cells was assessed by flow cytometry among 59 HIV-negative and 376 HIV-infected (185 hepatitis C coinfected) women in the Women's Interagency HIV Study. T-cell activation was defined by CD8⁺CD38⁺DR+ and CD4⁺CD3⁺8DR+. Multiple activation assessments over 6.5 years were averaged. In 140 women, T-cell activation was measured before and after highly active antiretroviral therapy (HAART) initiation. Carotid artery ultrasounds were completed a median of 6.5 years after last measurement of T-cell activation and carotid artery stiffness including distensibility and elasticity were calculated.ResultsPercentages of CD4⁺ and CD8⁺ T-cell activation were significantly higher in HIV- infected compared with HIV-negative women. Among HIV-negative women, T-cell activation was not associated with carotid artery stiffness. Among HIV-infected women, higher CD4⁺ T-cell activation levels significantly predicted increased arterial stiffness independent of CD4⁺ cell count and HIV RNA. The association was stronger among HIV/hepatitis C-coinfected women compared with HIV-monoinfected women; however, the difference was not statistically significant (P for interaction >0.05). Pre- and post-HAART levels of CD4⁺ T-cell activation significantly predicted carotid artery stiffness.ConclusionsPersistent T-cell activation, even after HAART initiation, can contribute to structural and/or functional vascular damage accelerating atherogenesis in HIV infection. These results need to be confirmed in a longitudinal prospective study.