title: Changes in plasma levels of oxidized lipoproteins and lipoprotein subfractions with atazanavir-, raltegravir-, darunavir-based initial antiviral therapy and associations with common carotid artery intima-media thickness: ACTG 5260s.
abstract: BACKGROUND
  The role of oxidized lipoproteins (high-density [HDLox] and low-density [LDLox]) and total lipoprotein particle (Lp) number and size in HIV-related cardiovascular disease (CVD) is unclear. The goal of this study was to evaluate changes of these biomarkers and their associations with rate of carotid intima media thickness progression over 3 years (ΔCIMT) in chronic HIV infection.
  
  
  METHODS
  Prospective study of 234 HIV-infected antiretroviral treatment-naive participants without CVD who were randomized to receive tenofovir-emtricitabine plus atazanavir/ritonavir, darunavir/ritonavir or raltegravir (RAL) and achieved plasma HIV-1 RNA <50 copies/ml by week 24 and thereafter. Biomarker changes over 24, 48 or 96 weeks from baseline and pairwise treatment group comparisons were examined. Associations of these biomarkers with ΔCIMT were analysed with mixed effects linear regression.
  
  
  RESULTS
  HDLp number increased with both protease inhibitors (PIs) over 48 weeks, while LDLp number declined with RAL; Lp size did not change. Over 96 weeks, normalized HDLox declined with both PIs; LDLox increased in all groups. Few treatment group differences were observed across all biomarkers. Associations between ΔCIMT and oxidized lipoproteins at all time points were not apparent (P≥0.10). There was some evidence of slower ΔCIMT for higher HDLp number (P=0.06) and for lower LDLp number (P=0.08) measured at baseline.
  
  
  CONCLUSIONS
  Unexpectedly, LDLox increased modestly in all treatment groups after ART initiation. Associations of plasma HDLox and LDLox with ΔCIMT were not apparent. While plasma levels of abnormal lipoproteins have been shown to be associated with CVD outcomes, clear associations with sub-clinical atherosclerosis progression were not apparent in our study.
authors.affiliation: David Geffen School of Medicine at University of California - Los Angeles, Los Angeles, CA, USA.
authors.forename: Theodoros
authors.initials: T
authors.lastname: Kelesidis
authors.affiliation: Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
authors.forename: Thuy Tien T
authors.initials: TTT
authors.lastname: Tran
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Todd T
authors.initials: TT
authors.lastname: Brown
authors.affiliation: Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
authors.forename: Carlee
authors.initials: C
authors.lastname: Moser
authors.affiliation: Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Ribaudo
authors.affiliation: Keck School of Medicine at the University of Southern California, Los Angeles, CA, USA.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Dube
authors.affiliation: David Geffen School of Medicine at University of California - Los Angeles, Los Angeles, CA, USA.
authors.forename: Otto O
authors.initials: OO
authors.lastname: Yang
authors.affiliation: Case Western Reserve University School of Medicine, Cleveland, OH, USA.|University Hospitals Case Medical Center, Cleveland, OH, USA.
authors.forename: Grace A
authors.initials: GA
authors.lastname: McComsey
authors.affiliation: University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: James H
authors.initials: JH
authors.lastname: Stein
authors.affiliation: David Geffen School of Medicine at University of California - Los Angeles, Los Angeles, CA, USA.
authors.forename: Judith S
authors.initials: JS
authors.lastname: Currier
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D000069446:Atazanavir Sulfate / Q000627:therapeutic use*; D059168:Carotid Intima-Media Thickness; D000069454:Darunavir / Q000627:therapeutic use*; D000068679:Emtricitabine / Q000627:therapeutic use; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics / Q000254:growth & development; D006801:Humans; D016014:Linear Models; D008075:Lipoproteins, HDL / Q000097:blood*; D008077:Lipoproteins, LDL / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D000068898:Raltegravir Potassium / Q000627:therapeutic use*; D019438:Ritonavir / Q000627:therapeutic use; D000068698:Tenofovir / Q000627:therapeutic use
chemical_list: D019380:Anti-HIV Agents; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D012367:RNA, Viral; C099252:oxidized low density lipoprotein; D000068898:Raltegravir Potassium; D000069446:Atazanavir Sulfate; D000068698:Tenofovir; D000068679:Emtricitabine; D019438:Ritonavir; D000069454:Darunavir