Abstract
Persons with HIV infection (PWH) have increased risk for cardiovascular disease (CVD), but the underlying mechanisms remain unclear. Coronary thrombosis is known to provoke myocardial infarctions, but whether PWH have elevated thrombotic propensity is unknown. We compared thrombogenicity of PWH on antiretroviral therapy versus matched controls using the Badimon chamber. Measures of inflammation, platelet reactivity, and innate immune activation were simultaneously performed. Enrolled PWH were then randomized to placebo, aspirin (81 mg), or clopidogrel (75 mg) for 24 weeks to assess treatment effects on study parameters. Thrombogenicity was significantly higher in PWH and correlated strongly with plasma levels of D-dimer, soluble TNF receptors 1 and 2, and circulating classical and nonclassical monocytes in PWH. Clopidogrel significantly reduced thrombogenicity and sCD14. Our data suggest that higher thrombogenicity, interacting with inflammatory and immune activation markers, contributes to the increased CVD risk observed in PWH. Clopidogrel exhibits an anti-inflammatory activity in addition to its antithrombotic effect in PWH.
Publication types
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Randomized Controlled Trial
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Anti-Inflammatory Agents / therapeutic use*
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Antiretroviral Therapy, Highly Active / methods
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Aspirin / therapeutic use*
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Biomarkers / blood
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Blood Platelets / drug effects*
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Blood Platelets / immunology
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Blood Platelets / virology
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Clopidogrel / therapeutic use*
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Coronary Thrombosis / complications
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Coronary Thrombosis / drug therapy*
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Coronary Thrombosis / immunology
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Coronary Thrombosis / virology
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Cross-Sectional Studies
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Female
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Fibrin Fibrinogen Degradation Products / genetics
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Fibrin Fibrinogen Degradation Products / immunology
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Gene Expression
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HIV Infections / complications
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HIV Infections / drug therapy*
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HIV Infections / immunology
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HIV Infections / virology
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Humans
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Immunity, Innate
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Inflammation
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Lipopolysaccharide Receptors / genetics
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Lipopolysaccharide Receptors / immunology
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Male
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Middle Aged
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Monocytes / drug effects
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Monocytes / immunology
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Monocytes / virology
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Platelet Aggregation / drug effects
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Platelet Aggregation Inhibitors / therapeutic use*
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Receptors, Tumor Necrosis Factor, Type I / genetics
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Receptors, Tumor Necrosis Factor, Type I / immunology
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Receptors, Tumor Necrosis Factor, Type II / genetics
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Receptors, Tumor Necrosis Factor, Type II / immunology
Substances
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Anti-Inflammatory Agents
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Biomarkers
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CD14 protein, human
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Fibrin Fibrinogen Degradation Products
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Lipopolysaccharide Receptors
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Platelet Aggregation Inhibitors
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Receptors, Tumor Necrosis Factor, Type I
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Receptors, Tumor Necrosis Factor, Type II
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fibrin fragment D
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Clopidogrel
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Aspirin