title: A prospective, randomized clinical trial of antiretroviral therapies on carotid wall thickness.
abstract: OBJECTIVE
  This article compares the effects of initiating three contemporary antiretroviral therapy (ART) regimens on progression of carotid artery intima-media thickness (IMT) over 3 years.
  
  
  METHODS
  Randomized clinical trial.
  
  
  METHODS
  Multicenter (26 institutions).
  
  
  METHODS
  ART-naive HIV-infected individuals (n = 328) without known cardiovascular disease or diabetes mellitus.
  
  
  METHODS
  Random assignment to tenofovir/emtricitabine along with atazanavir/ritonavir (ATV/r), darunavir/ritonavir (DRV/r), or raltegravir (RAL).
  
  
  METHODS
  Right-sided carotid IMT was evaluated by B-mode ultrasonography before ART initiation, and then after 48, 96, and 144 weeks. Comparisons of yearly rates of change in carotid IMT used mixed-effects linear regression models that permitted not only evaluation of the effects of ART on carotid IMT progression but also how ART-associated changes in traditional risk factors, bilirubin, and markers of HIV infection were associated carotid IMT progression.
  
  
  RESULTS
  HIV-1 RNA suppression rates were high in all arms (>85%) over 144 weeks. Modest increases in triglycerides and non-high-density lipoprotein cholesterol levels were observed in the protease inhibitor-containing arms compared with decreases with RAL. In contrast, carotid IMT progressed more slowly on ATV/r [8.2, 95% confidence interval (5.6, 10.8) μm/year] than DRV/r [12.9 (10.3, 15.5) μm/year, P = 0.013]; changes with RAL were intermediate [10.7 (9.2, 12.2) μm/year, P = 0.15 vs. ATV/r; P = 0.31 vs. DRV/r]. Bilirubin and non-high-density lipoprotein cholesterol levels appeared to influence carotid IMT progression rates.
  
  
  CONCLUSIONS
  In ART-naive HIV-infected individuals at low cardiovascular disease risk, carotid IMT progressed more slowly in participants initiating ATV/r than those initiating DRV/r, with intermediate changes associated with RAL. This effect may be due, in part, to hyperbilirubinemia.
authors.affiliation: aUniversity of Wisconsin School of Medicine and Public Health, Madison, Wisconsin bHarvard School of Public Health, Boston, Massachusetts cKeck School of Medicine, University of Southern California, Los Angeles, California dJohns Hopkins University School of Medicine, Baltimore, Maryland eCase School of Medicine, Cleveland, Ohio fFeinberg School of Medicine, Northwestern University, Chicago, Illinois gDavid Geffen School of Medicine, University of California-Los Angeles, Los Angeles, California, USA.
authors.forename: James H
authors.initials: JH
authors.lastname: Stein
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Ribaudo
authors.forename: Howard N
authors.initials: HN
authors.lastname: Hodis
authors.forename: Todd T
authors.initials: TT
authors.lastname: Brown
authors.forename: Thuy Tien T
authors.initials: TT
authors.lastname: Tran
authors.forename: Mingzhu
authors.initials: M
authors.lastname: Yan
authors.forename: Elizabeth Lauer
authors.initials: EL
authors.lastname: Brodell
authors.forename: Theodore
authors.initials: T
authors.lastname: Kelesidis
authors.forename: Grace A
authors.initials: GA
authors.lastname: McComsey
authors.forename: Michael P
authors.initials: MP
authors.lastname: Dube
authors.forename: Robert L
authors.initials: RL
authors.lastname: Murphy
authors.forename: Judith S
authors.initials: JS
authors.lastname: Currier
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D002339:Carotid Arteries / Q000000981:diagnostic imaging; D002340:Carotid Artery Diseases / Q000473:pathology*; D059168:Carotid Intima-Media Thickness; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies
chemical_list: D044966:Anti-Retroviral Agents