title: Changes in biomarkers in HIV-1-infected treatment-naive patients treated with tenofovir DF/emtricitabine plus atazanavir/ritonavir or lopinavir/ritonavir for 96 weeks: the CASTLE biomarker substudy.
abstract: BACKGROUND
  The impact of boosted protease inhibitor therapy on inflammatory and cardiovascular biomarker levels in treatment-naive HIV-infected patients remains unclear and may differ between agents. Unconjugated bilirubin elevation, which favourably affects vascular biomarkers and cardiovascular disease risk in Gilbert's syndrome, occurs with atazanavir.
  
  
  METHODS
  CASTLE was a 96-week study comparing efficacy and safety in treatment-naive HIV-1-infected patients randomized to atazanavir/ritonavir (ATV/r) versus lopinavir/ritonavir (LPV/r), each in combination with tenofovir disoproxil fumarate/emtricitabine. In this substudy, fasting plasma tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), high sensitivity C-reactive protein (hs-CRP), plasminogen activator inhibitor-1 (PAI-1) and fibrinogen were assessed at baseline, week 12, 24, 48 and 96. Impact of grade 3-4 hyperbilirubinaemia on biomarkers was examined.
  
  
  RESULTS
  CASTLE demonstrated similar efficacy in both treatment arms with higher rates of hyperbilirubinaemia on ATV/r and elevated lipids on LPV/r. In this substudy (n=224), patterns of biomarker expression were similar between the ATV/r and LPV/r groups and between-group differences in biomarker percentage change from baseline were not significant at 48 and/or 96 weeks. Hyperbilirubinaemia did not influence fasting biomarker expression.
  
  
  CONCLUSIONS
  No significant differences were noted between ATV/r and LPV/r for biomarker percentage changes from baseline. Furthermore, no association was found between total bilirubin levels and biomarker expression.
authors.affiliation: Chelsea and Westminster Hospital, London, UK. gm@moyleg.demon.co.uk.
authors.forename: Graeme
authors.initials: G
authors.lastname: Moyle
authors.forename: Helene
authors.initials: H
authors.lastname: Hardy
authors.forename: Jonathan
authors.initials: J
authors.lastname: Uy
authors.forename: Neelanjana
authors.initials: N
authors.lastname: Ray
authors.forename: Maria Jesus
authors.initials: MJ
authors.lastname: Jimenez-Exposito
authors.forename: Donnie
authors.initials: D
authors.lastname: McGrath
authors.forename: Edwin
authors.initials: E
authors.lastname: DeJesus
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D015415:Biomarkers / Q000097:blood; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D008297:Male; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D015415:Biomarkers