Browsing by Author "Stein, James H."

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    GCH1 haplotypes and cardiovascular risk in HIV
    (Wolters Kluwer, 2019-05) Slaven, James E.; Haas, David W.; Liu, Ziyue; Stein, James H.; Brown, Todd T.; Gupta, Samir K.; Biostatistics, School of Public Health
    Heightened systemic inflammation contributes to cardiovascular (CVD) events in people living with HIV (PLWH), though not all PLWH develop CVD, thus suggesting a genetic modifying role. We examined GCH1 polymorphisms, which have been associated with reduced endothelial function in European populations with CVD and increased inflammation, in a racially diverse cohort of U.S. PLWH initiating antiretroviral therapy (ART). GCH1 polymorphisms differed by race and were not associated flow-mediated dilation or carotid intima media thickness before or after 48 weeks of ART.
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    HIV infection, antiretroviral therapy, and measures of endothelial function, inflammation, metabolism, and oxidative stress
    (PLOS, 2017-08-17) Dysangco, Andrew; Liu, Ziyue; Stein, James H.; Dubé, Michael P.; Gupta, Samir K.; Medicine, School of Medicine
    Background HIV-infected patients have an increased risk of cardiovascular disease (CVD). Impaired endothelial function is an early risk factor for CVD in the general population. It is presumed that HIV infection is associated with impaired endothelial function, but results have been inconsistent. Objectives Our objectives were to determine the relationships between HIV infection, virologic suppression with antiretroviral therapy (ART), in vivo measures of conduit artery and microvascular endothelial function, and circulating biomarkers of pathways associated with CVD. Methods We performed a cross-sectional analysis of three prospectively enrolled groups from a single center: 28 were HIV-infected and virologically-suppressed on a regimen of FTC/TDF/EFV (HIV+ART+), 44 were HIV-infected but not on ART (HIV+ART-), and 39 were HIV-uninfected healthy volunteers (HIV-) matched to the HIV+ART- group for age, sex, smoking status, and height. None had diabetes, uncontrolled hypertension, known CVD, or other pro-inflammatory condition. Flow mediated dilation (FMD), nitroglycerin-mediated dilation (NTGMD), reactive hyperemia velocity time integral (RHVTI), and FMD/RHVTI of the brachial artery were measured, as well as circulating biomarkers of systemic inflammation, metabolism, oxidative stress, and endothelial activation. Results No significant differences were found amongst the three groups in FMD (P = 0.46), NTGMD (P = 0.42), RHVTI (P = 0.17), and FMD/RHVTI (P = 0.22) in unadjusted comparisons. Adjusted ANOVA models which included brachial artery diameter, demographics, and conventional CVD risk factors did not appreciably change these findings. In pairwise comparisons, the HIV+ART- group had significantly higher soluble tumor necrosis factor receptor II, soluble CD163, β-2 microglobulin, interferon-γ- induced protein-10, tissue inhibitor of metalloproteinase-1, and vascular cell adhesion molecule-1 compared to the other two groups (all p<0.05). Correlates of endothelial function differed between study groups. Conclusion Although untreated HIV infection was associated with elevated levels of several biomarkers of inflammation and endothelial activation, we were unable to demonstrate differences in measures of conduit artery and microvascular endothelial function in this study population.
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    Microbial translocation and metabolic and body composition measures in treated and untreated HIV infection
    (Mary Ann Liebert, Inc., 2014-03) Timmons, Tamara; Shen, Changyu; Aldrovandi, Grace; Rollie, Adrienne; Gupta, Samir K.; Stein, James H.; Dube´, Michael P.; Biostatistics, School of Medicine
    Circulating levels of microbial products such as lipopolysaccharide (LPS) are increased in HIV infection. Microbial translocation promotes obesity, insulin resistance, and dyslipidemia in other settings. We examined data from 178 subjects: an Indiana University (IU) cross-sectional study [N=49 on antiretroviral therapy (ART), N=47 not on ART], and a 24 week prospective study of ART initiation ACTG 5152s (N=82). Pearson correlations were used to describe relationships of plasma LPS levels and soluble CD14 (sCD14), a marker of monocyte activation, with metabolic and body composition measures. HOMA-IR (a measure of insulin resistance) and LPS were correlated for the combined cohorts (r=0.19, p=0.02), particularly in the 5152s ART-naive cohort (r=0.41, p<0.01). Triglycerides were correlated with LPS in the combined cohort (r=0.32, p<0.01), and all subsets excluding the IU on ART subset. There were negative correlations between sCD14 and high-density lipoprotein (HDL) cholesterol in all subjects (r=-0.21, p<0.01), as well as the IU subset not on ART (r=-0.32, p=0.04). Large particle HDL as measured by NMR spectroscopy, but not HDL cholesterol, was negatively correlated with LPS (r=-0.18, p=0.02), particularly among the IU subset receiving ART (r=-0.33, p=0.03). In the combined cohorts, sCD14 was negatively correlated with lean mass as well as trunk and limb fat. There is a relationship between microbial translocation markers and metabolic effects, particularly lipoproteins. During prolonged ART, microbial translocation was associated with an adverse effect on large HDL and thus may contribute to the increased cardiovascular disease risk observed during chronic treatment of HIV.
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    A Pilot Trial of Pentoxifylline on Endothelial Function and Inflammation in HIV-infected Patients Initiating Antiretroviral Therapy
    (Wolters Kluwer, 2016-08-24) Gupta, Samir K.; Dubé, Michael P.; Stein, James H.; Clauss, Matthias A.; Liu, Ziyue; Medicine, School of Medicine