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Conflicting effects of atazanavir therapy on atherosclerotic risk factors in stable HIV patients: A randomized trial of regimen switch to atazanavir.

Conflicting effects of atazanavir therapy on atherosclerotic risk factors in stable HIV patients: A randomized trial of regimen switch to atazanavir.
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Beckman JA, Wood BR, Ard KL, Price CN, Solomon DA, Zuflacht JP, Milian J, Prenner JC, Sax PE,


Beckman JA, Wood BR, Ard KL, Price CN, Solomon DA, Zuflacht JP, Milian J, Prenner JC, Sax PE, (click to view)

Beckman JA, Wood BR, Ard KL, Price CN, Solomon DA, Zuflacht JP, Milian J, Prenner JC, Sax PE,

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PloS one 2017 10 1212(10) e0181993 doi 10.1371/journal.pone.0181993

Abstract

Bilirubin acts as a potent endogenous antioxidant, with higher concentrations associated with lower rates of CVD; the antiretroviral drug atazanavir (ATV) increases bilirubin levels but may also increase von Willebrand factor levels. We tested the hypothesis that increasing endogenous bilirubin using ATV would improve cardiometabolic risk factors and vascular function in older patients with HIV. Ninety participants were enrolled in two study protocols. In protocol 1, we evaluated markers of inflammation, thrombosis, and conduit artery endothelial function in subjects on non-ATV containing regimens. Participants were randomly assigned to continue baseline treatment or switch to an ATV-based regimen. Measurements were made at baseline and 28 days. In the protocol 2, we enrolled 30 subjects who received atazanavir for more than one year and were compared to the aim 1 protocol subjects at baseline. 60 subjects were enrolled in the first protocol (mean age 53, +/- 6 years), with 31 randomized to ATV and 29 continuing baseline treatment. Atazanavir significantly increased serum total bilirubin levels (p<0.001) and acutely but not chronically plasma total antioxidant capacity (p<0.001). An increase in von Willebrand Factor (p<0.001) and reduction in hs-CRP (p = 0.034) were noted. No changes were seen in either flow-mediated endothelium-dependent or vasodilation. In cross-sectional analysis (second protocol), similar findings were seen in the baseline attributes of non-atazanavir-based and long-term atazanavir users. Increasing serum bilirubin levels with atazanavir in subjects with HIV reduces hs-CRP, temporarily reduces oxidative stress, but increases von Willebrand Factor. Atazanavir does not improve endothelial function of conduit arteries. TRIAL REGISTRATION
ClinicalTrials.gov NCT03019783.

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