Roksana Karim1, Wendy J Mack, Naoko Kono, Phyllis C Tien, Kathryn Anastos, Jason Lazar, Mary Young, Seema Desai, Elizabeth T Golub, Robert C Kaplan, Howard N Hodis, Andrea Kovacs. 1. *Maternal, Child and Adolescent Center for Infectious Disease and Virology, Department of Pediatrics, University of Southern California, Los Angeles, CA; †Department of Preventive Medicine, University of Southern California, Los Angeles, CA; ‡Atherosclerosis Research Unit, University of Southern California, Los Angeles, CA; §Department of Medicine, University of California, San Francisco, San Francisco, CA; ‖Medical Service, Department of Veterans Affairs, University of California, San Francisco, San Francisco, CA; ¶Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY; #Division of Cardiovascular Medicine, State University of New York Downstate Medical Center, Brooklyn, NY; **Georgetown University Medical Center, Georgetown University, Washington, DC; ††Departments of Medicine, Stroger Hospital and Rush University, Chicago, IL; ‡‡Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; and §§Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY.
Abstract
OBJECTIVE: T-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. DESIGN: Linear regression models evaluated the covariate-adjusted association of T-cell activation with vascular stiffness. METHODS: CD38 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. RESULTS: Percentages 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. CONCLUSIONS: Persistent 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.
OBJECTIVE: T-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. DESIGN: Linear regression models evaluated the covariate-adjusted association of T-cell activation with vascular stiffness. METHODS:CD38 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. RESULTS: Percentages 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-infectedwomen, 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-coinfectedwomen 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. CONCLUSIONS: Persistent 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.
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