Targeting thrombogenicity and inflammation in chronic HIV infection

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.

Association of intestinal and systemic inflammatory biomarkers with immune reconstitution in HIV+ patients on ART

“…In the Multicenter AIDS Cohort Study (MACS) and other recent studies, it has been reported that levels of inflammation and immune activation biomarkers, including sCD163, decrease after ART initiation [33]. In our study, we have not detected significant differences in the concentrations of sCD163 among groups; however, this is consistent with previous reports that did not find persistently elevated levels of sCD163 in HIV+ patients on ART [32][33][34][35][36].…”

Incidence of Venous Thromboembolism in Patients Living with HIV: A Cohort Study

“…1 In a systematic review, Klein et al report higher incidence of VTE in HIV, ranging from <1% to 18% in one small study of 60 HIV-positive patients. 2 Several risk factors have been described for VTE in HIV, such as antiretroviral medication, 3,4 chronic low-level inflammation, 5 opportunistic infections, AIDS status, and cancer. 6,7 To our knowledge, there is no population-based study estimating both outpatient and inpatient incidence of VTE in HIV-positive versus a comparable population of HIV-negative patients.…”

HIV-Related Immune Activation and Inflammation: Current Understanding and Strategies

“…Increased platelet activity has been reported in ART-treated HIV infection, and in vitro studies showed that HIV-1 plasma could activate healthy platelets, which in turn activated monocytes, implicating a direct role for activated platelets in immune activation [ 123 ]. In addition, a higher thrombogenicity and inflammation/immune activation contribute to the increased cardiovascular disease risk in PLWH [ 124 ]. Therefore, antiplatelet agents were tried in ART-experienced patients.…”