Potential cardiovascular disease risk markers among HIV-infected women initiating antiretroviral treatment

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

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38 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)359-368
Number of pages10
JournalJournal of Acquired Immune Deficiency Syndromes
Volume60
Issue number4
DOIs
StatePublished - Aug 1 2012

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Keywords

  • HIV
  • antiretroviral therapy
  • cardiovascular diseases
  • cytokines
  • hemostasis
  • inflammation

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

Cite this

Kaplan, R. C., Landay, A. L., Hodis, H. N., Gange, S. J., Norris, P. J., Young, M., Anastos, K., Tien, P. C., Xue, X., Lazar, J., Parrinello, C. M., Benning, L., & Tracy, R. P. (2012). Potential cardiovascular disease risk markers among HIV-infected women initiating antiretroviral treatment. Journal of Acquired Immune Deficiency Syndromes, 60(4), 359-368. https://doi.org/10.1097/QAI.0b013e31825b03be