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

Research output: Contribution to journalArticle

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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Cardiovascular Diseases
Highly Active Antiretroviral Therapy
HIV
Interleukin-2 Receptors
Tumor Necrosis Factor-alpha
Hemostasis
Interleukin-10
Therapeutics
Carotid Intima-Media Thickness
Chemokine CCL2
Biomarkers
Carotid Arteries
HIV Infections
Interleukin-6
Atherosclerosis
Inflammation
Fibrinogen
Blood Vessels
fibrin fragment D

Keywords

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

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

Cite this

Potential cardiovascular disease risk markers among HIV-infected women initiating antiretroviral treatment. / Kaplan, Robert C.; Landay, Alan L.; Hodis, Howard N.; Gange, Stephen J; Norris, Philip J.; Young, Mary; Anastos, Kathryn; Tien, Phyllis C.; Xue, Xiaonan; Lazar, Jason; Parrinello, Christina M.; Benning, Lorie; Tracy, Russell P.

In: Journal of Acquired Immune Deficiency Syndromes, Vol. 60, No. 4, 01.08.2012, p. 359-368.

Research output: Contribution to journalArticle

Kaplan, RC, Landay, AL, Hodis, HN, Gange, SJ, Norris, PJ, Young, M, Anastos, K, Tien, PC, Xue, X, Lazar, J, Parrinello, CM, Benning, L & Tracy, RP 2012, 'Potential cardiovascular disease risk markers among HIV-infected women initiating antiretroviral treatment', Journal of Acquired Immune Deficiency Syndromes, vol. 60, no. 4, pp. 359-368. https://doi.org/10.1097/QAI.0b013e31825b03be
Kaplan, Robert C. ; Landay, Alan L. ; Hodis, Howard N. ; Gange, Stephen J ; Norris, Philip J. ; Young, Mary ; Anastos, Kathryn ; Tien, Phyllis C. ; Xue, Xiaonan ; Lazar, Jason ; Parrinello, Christina M. ; Benning, Lorie ; Tracy, Russell P. / Potential cardiovascular disease risk markers among HIV-infected women initiating antiretroviral treatment. In: Journal of Acquired Immune Deficiency Syndromes. 2012 ; Vol. 60, No. 4. pp. 359-368.
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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.",
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AU - Kaplan, Robert C.

AU - Landay, Alan L.

AU - Hodis, Howard N.

AU - Gange, Stephen J

AU - Norris, Philip J.

AU - Young, Mary

AU - Anastos, Kathryn

AU - Tien, Phyllis C.

AU - Xue, Xiaonan

AU - Lazar, Jason

AU - Parrinello, Christina M.

AU - Benning, Lorie

AU - Tracy, Russell P.

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N2 - 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.

AB - 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.

KW - antiretroviral therapy

KW - cardiovascular diseases

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