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

Autor: Beckman JA; Cardiovascular Division, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America., Wood BR; Division of Infectious Disease, Brigham and Women's Hospital, Boston, Massachusetts, United States of America., Ard KL; Division of Infectious Disease, Brigham and Women's Hospital, Boston, Massachusetts, United States of America., Price CN; Division of Infectious Disease, Brigham and Women's Hospital, Boston, Massachusetts, United States of America., Solomon DA; Division of Infectious Disease, Brigham and Women's Hospital, Boston, Massachusetts, United States of America., Zuflacht JP; Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts, United States of America., Milian J; Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts, United States of America., Prenner JC; Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts, United States of America., Sax PE; Division of Infectious Disease, Brigham and Women's Hospital, Boston, Massachusetts, United States of America.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2017 Oct 12; Vol. 12 (10), pp. e0181993. Date of Electronic Publication: 2017 Oct 12 (Print Publication: 2017).
DOI: 10.1371/journal.pone.0181993
Abstrakt: 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.
Databáze: MEDLINE
Externí odkaz: