title: 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.
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.
  
  
  METHODS
  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.
authors.affiliation: *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.
authors.forename: Roksana
authors.initials: R
authors.lastname: Karim
authors.forename: Wendy J
authors.initials: WJ
authors.lastname: Mack
authors.forename: Naoko
authors.initials: N
authors.lastname: Kono
authors.forename: Phyllis C
authors.initials: PC
authors.lastname: Tien
authors.forename: Kathryn
authors.initials: K
authors.lastname: Anastos
authors.forename: Jason
authors.initials: J
authors.lastname: Lazar
authors.forename: Mary
authors.initials: M
authors.lastname: Young
authors.forename: Seema
authors.initials: S
authors.lastname: Desai
authors.forename: Elizabeth T
authors.initials: ET
authors.lastname: Golub
authors.forename: Robert C
authors.initials: RC
authors.lastname: Kaplan
authors.forename: Howard N
authors.initials: HN
authors.lastname: Hodis
authors.forename: Andrea
authors.initials: A
authors.lastname: Kovacs
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002340:Carotid Artery Diseases / Q000503:physiopathology*; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology; D018023:HIV Seronegativity / Q000276:immunology; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D016014:Linear Models; D008213:Lymphocyte Activation; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D059289:Vascular Stiffness
chemical_list: D006684:HLA-DR Antigens; D051997:ADP-ribosyl Cyclase 1