Institutional members access full text with Ovid®

Share this article on:

Potential Cardiovascular Disease Risk Markers Among HIV-Infected Women Initiating Antiretroviral Treatment

Kaplan, Robert C. PhD; Landay, Alan L. PhD; Hodis, Howard N. MD; Gange, Stephen J. PhD; Norris, Philip J. MD; Young, Mary MD; Anastos, Kathryn MD; Tien, Phyllis C. MD; Xue, Xiaonan PhD; Lazar, Jason MD, MPH; Parrinello, Christina M. MPH; Benning, Lorie MS; Tracy, Russell P. PhD

JAIDS Journal of Acquired Immune Deficiency Syndromes: August 1st, 2012 - Volume 60 - Issue 4 - p 359–368
doi: 10.1097/QAI.0b013e31825b03be
Clinical Science

Background: Inflammation and hemostasis perturbation may be involved in vascular complications of HIV infection. We examined atherogenic biomarkers and subclinical atherosclerosis in HIV-infected adults before and after beginning highly active antiretroviral therapy (HAART).

Methods: In the Women's Interagency HIV Study, 127 HIV-infected women studied pre and post HAART were matched to HIV-uninfected controls. Six semiannual measurements of soluble CD14, tumor necrosis factor (TNF) alfa, soluble interleukin (IL) 2 receptor, IL-6, IL-10, monocyte chemoattractant protein 1, D-dimer, and fibrinogen were obtained. Carotid artery intima–media thickness was measured by B-mode ultrasound.

Results: Relative to HIV-uninfected controls, HAART-naive HIV-infected women had elevated levels of soluble CD14 (1945 vs 1662 ng/mL, Wilcoxon signed rank P < 0.0001), TNF-α (6.3 vs 3.4 pg/mL, P < 0.0001), soluble IL-2 receptor (1587 vs 949 pg/mL, P < 0.0001), IL-10 (3.3 vs 1.9 pg/mL, P < 0.0001), monocyte chemoattractant protein 1 (190 vs 163 pg/mL, P < 0.0001), and D-dimer (0.43 vs 0.31 μg/mL, P < 0.01). Elevated biomarker levels declined after HAART. Although most biomarkers normalized to HIV-uninfected levels, in women on effective HAART, TNF-α levels remained elevated compared with HIV-uninfected women (+0.8 pg/mL, P = 0.0002). Higher post-HAART levels of soluble IL-2 receptor (P = 0.02), IL-6 (P = 0.05), and D-dimer (P = 0.03) were associated with increased carotid artery intima–media thickness.

Conclusions: Untreated HIV infection is associated with abnormal hemostasis (eg, D-dimer), proatherogenic (eg, TNF-α), and antiatherogenic (eg, IL-10) inflammatory markers. HAART reduces most inflammatory mediators to HIV-uninfected levels. Increased inflammation and hemostasis are associated with subclinical atherosclerosis in recently treated women. These findings have potential implications for long-term risk of cardiovascular disease in HIV-infected patients, even with effective therapy.

*Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY

Department of Immunology/Microbiology, Rush University Medical Center

Atherosclerosis Research Unit, University of Southern California

§Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD

Department of Laboratory Medicine, Blood Systems Research Institute, University of California, San Francisco, San Francisco, CA

Department of Medicine, Georgetown University Medical Center, Washington, DC

#Department of Medicine, University of California, San Francisco, San Francisco, CA

**San Francisco Veterans Affairs Medical Center, San Francisco, CA

††Department of Medicine, State University of New York, Downstate Medical Center, Brooklyn, NY

Departments of ‡‡Pathology

§§Biochemistry, University of Vermont College of Medicine, Burlington, VT

Correspondence to: Robert C. Kaplan, PhD, Department of Epidemiology and Population Health, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Belfer 1306C, Bronx, NY 10461 (e-mail:

Supported by the National Institutes of Health. The Women's Interagency HIV Study 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 was cofunded by the National Cancer Institute, the National Institute on Drug Abuse, and the National Institute on Deafness and Other Communication Disorders. Funding was also provided by the National Center for Research Resources (UCSF-CTSI Grant Number UL1 RR024131). Additional cofunding was provided by the National Heart, Lung and Blood Institute (1R01HL095140, 1R01HL083760 to R.C.K.). Partial funding for laboratory work and assistance with general study coordination was provided by the University of Washington's CVD and Metabolic Complications of HIV/AIDS Data Coordinating Center (5R01HL095126).

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.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (

Received August 31, 2011

Accepted April 17, 2012

Copyright © 2012 Wolters Kluwer Health, Inc. All rights reserved.