Browsing by Author "Dubé, Michael P."

Now showing 1 - 6 of 6
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    Effects of switching from efavirenz to raltegravir on endothelial function, bone mineral metabolism, inflammation, and renal function: a randomized, controlled trial
    (Wolters Kluwer, 2013-11) Gupta, Samir K.; Mi, Deming; Moe, Sharon M.; Dubé, Michael P.; Liu, Ziyue; Medicine, School of Medicine
    We performed a randomized controlled trial in 30 HIV-infected participants to either continue tenofovir/emtricitabine/efavirenz (Continuation Group) or switch to tenofovir/emtricitabine/raltegravir (Switch Group) for 24 weeks. There were no significant differences in the changes in flow-mediated dilation, 25(OH) vitamin D, or parathyroid hormone levels. Total cholesterol, high sensitivity C-reactive protein, serum alkaline phosphatase, sCD14 levels, and renal function significantly declined in the Switch Group compared with the Continuation Group; however, sCD163 levels significantly increased in the Switch Group. These findings suggest that raltegravir is not inherently more beneficial to endothelial function compared with efavirenz but may impact renal function and monocyte activation.
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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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    Pentoxifylline, Inflammation, and Endothelial Function in HIV-Infected Persons: A Randomized, Placebo-Controlled Trial
    (Public Library of Science, 2013-04-09) Gupta, Samir K.; Mi, Deming; Dubé, Michael P.; Saha, Chandan K.; Johnson, Raymond M.; Stein, James H.; Clauss, Matthias A.; Mather, Kieren J.; Desta, Zeruesenay; Liu, Ziyue; Medicine, School of Medicine
    Background: Untreated HIV may increase the risk of cardiovascular events. Our preliminary in vitro and in vivo research suggests that pentoxifylline (PTX) reduces vascular inflammation and improves endothelial function in HIV-infected persons not requiring antiretroviral therapy. Methods: We performed a randomized, placebo-controlled trial of PTX 400 mg orally thrice daily for 8 weeks in 26 participants. The primary endpoint was change in flow-mediated dilation (FMD) of the brachial artery after 8 weeks. Nitroglycerin-mediated dilation (NTGMD) and circulating markers of inflammation, cellular immune activation, coagulation, and metabolism were also assessed. Results: The difference in mean absolute change (SD) in FMD after 8 weeks between the placebo [-1.06 (1.45)%] and PTX [-1.93 (3.03)%] groups was not significant (P = 0.44). No differences in NTGMD were observed. The only significant between-group difference in the changes in biomarkers from baseline to week 8 was in soluble tumor necrosis factor receptor-1 (sTNFRI) [-83.2 pg/mL in the placebo group vs. +65.9 pg/mL in the PTX group; P = 0.03]. PTX was generally well-tolerated. Conclusions: PTX did not improve endothelial function and unexpectedly increased the inflammatory biomarker sTNFRI in HIV-infected participants not requiring antiretroviral therapy. Additional interventional research is needed to reduce inflammation and cardiovascular risk in this population.
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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
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    Relationship between Microbial Translocation and Endothelial Function in HIV Infected Patients
    (Public Library of Science, 2012) Blodget, Emily; Shen, Changyu; Aldrovandi, Grace; Rollie, Adrienne; Gupta, Samir K.; Stein, James H.; Dubé, Michael P.; Medicine, School of Medicine
    Background: Circulating levels of microbial products are increased in HIV infection, and provoke endothelial dysfunction in other disease settings. Methodology/principal findings: We examined data from a cross-sectional single site study at Indiana University (Indiana, N = 85) and a 24- week multicenter prospective study of antiretroviral therapy (ART) initiation (ACTG 5152s, N = 75). Brachial artery flow-mediated dilation (FMD) was measured by ultrasound. Plasma lipopolysaccharide (LPS) and soluble CD14 (sCD14) levels were measured from stored specimens and correlated with FMD values using Pearson correlations. The Indiana subjects were 63% male with a mean age of 39 years and a median CD4 count of 406 cells/mm(3) (388 not on ART, 464 on ART). The 5152s subjects were 92% were male with a mean age of 35 years and a median CD4 count of 251 cells/mm(3) at entry which increased to 396 cells/mm(3) on ART. When analyzing the two cohorts individually or in combination neither sCD14 nor LPS correlated significantly with FMD. In a pre-specified subgroup analysis of the Indiana subjects receiving ART (N = 46, mean ART duration 40 months) LPS was inversely correlated with FMD (r = -0.33, p = 0.02), but not sCD14 (r = -0.01, p = 0.9). Multivariate analysis confirmed LPS as an independent predictor of FMD in this subgroup (p = 0.02). Conclusions/significance: In HIV-infected individuals on prolonged ART, higher LPS levels are associated with worse endothelial function but not in untreated subjects or at 24 weeks after ART initiation. Persistent microbial translocation may contribute to arterial dysfunction and the increased cardiovascular disease risk observed in individuals on long-term ART.
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    Worsening Endothelial Function with Efavirenz Compared to Protease Inhibitors: A 12-Month Prospective Study
    (Public Library of Science, 2012) Gupta, Samir K.; Shen, Changyu; Moe, Sharon M.; Kamendulis, Lisa M.; Goldman, Mitchell; Dubé, Michael P.; Medicine, School of Medicine
    Objective: Changes in endothelial function, measured as flow-mediated dilation (FMD) of the brachial artery, has not been systematically assessed beyond 6 months of initiation of antiretroviral therapy (ART) when drug-related effects might offset initial improvements with virologic control. Design: We assessed 6 and 12 month changes in FMD [presented as median (quartile 1, quartile 3)] and circulating HIV and cardiovascular biomarkers in 23 subjects initiating ART. Results: There were no significant changes in FMD at 6 or 12 months overall despite significant increases in CD4 cell count and HDL-C and reductions in HIV RNA level, MCP-1, IP-10, sVCAM-1, sTNFR2, and sCD14. However, there were significant differences (P = 0.04) in the changes in FMD between those receiving efavirenz [N = 12; -3.50% (-4.90%, 0.68%)] vs. protease inhibitors at 12 months [N = 11; 1.50% (-0.86%, 4.56%)]. The differences in changes in FMD between those receiving and not receiving emtricitabine/tenofovir/efavirenz were more pronounced and were significantly different at both 6 and 12 months (P<0.02 for both). Additional studies showed no significant differences in changes in 25-(OH)-vitamin D, PTH, FGF-23, of F2-isoprostane levels between efavirenz and PI use or between those receiving and not receiving emtricitabine/tenofovir/efavirenz. Conclusion: Efavirenz use was associated with reduced FMD at 12 months compared to PI-based regimens while emtricitabine/tenofovir/efavirenz was associated with reduced FMD at both 6 and 12 months compared to those not receiving this combination. Long-term effects of antiretrovirals on endothelial function may play an important role in the risk of cardiovascular disease in HIV-infected patients.