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

Antivir Ther. 2014;19(7):693-9. doi: 10.3851/IMP2778. Epub 2014 Apr 16.

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.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active
  • Biomarkers / blood
  • Drug Therapy, Combination
  • Female
  • HIV Infections / blood*
  • HIV Infections / diagnosis
  • HIV Infections / drug therapy*
  • HIV-1* / drug effects
  • Humans
  • Male
  • Time Factors
  • Treatment Outcome
  • Young Adult

Substances

  • Anti-HIV Agents
  • Biomarkers