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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

Karim, Roksana MBBS, PhD*,†,‡; Mack, Wendy J. PhD†,‡; Kono, Naoko MPH; Tien, Phyllis C. MD§,‖; Anastos, Kathryn MD; Lazar, Jason MD#; Young, Mary MD**; Desai, Seema PhD††; Golub, Elizabeth T. PhD‡‡; Kaplan, Robert C. PhD§§; Hodis, Howard N. MD†,‡; Kovacs, Andrea MD*

JAIDS Journal of Acquired Immune Deficiency Syndromes: 1 November 2014 - Volume 67 - Issue 3 - p 349–356
doi: 10.1097/QAI.0000000000000311
Epidemiology and Prevention

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+CD38+DR+. 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.

*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.

Correspondence to: Roksana Karim, MBBS, PhD, Departments of Pediatrics and Preventive Medicine, University of Southern California, 2001 N Soto St., SSB 312-F, Los Angeles, CA 90032 (e-mail: rkarim@usc.edu).

Data in this article were collected by the Women's Interagency HIV Study (WIHS) Collaborative Study Group with centers (Principal Investigators) at New York City/Bronx Consortium (K.A.); Brooklyn, NY (Howard Minkoff); Washington DC, Metropolitan Consortium (M.Y.); The Connie Wofsy Study Consortium of Northern California (Ruth Greenblatt); Los Angeles County/Southern California Consortium (Alexandra Levine); Chicago Consortium (Mardge Cohen); Data Coordinating Center (Stephen Gange). The WIHS is funded by the National Institute of Allergy and Infectious Diseases (UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, and UO1-AI-42590) and by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (UO1- HD-32632). The study is co-funded by the National Cancer Institute, the National Institute on Drug Abuse, and the National Institute on Deafness and Other Communication Disorders. Funding is also provided by the National Center for Research Resources (UCSF-CTSI Grant UL1 RR024131), NIH 2 R01 AI 52065, 1R01HL083760-01 from NHLBI/NIH, and R21 HL120394 NHLBI/NIH.

Presented previously at the American Heart Association Epidemiology and Prevention/Nutrition, Physical Activity and Metabolism Scientific Sessions, March 13–16, 2012, San Diego, CA.

The authors have no conflicts of interest to disclose.

The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health.

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Received February 21, 2014

Accepted July 07, 2014

© 2014 by Lippincott Williams & Wilkins