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Switch to RAL-containing regimen
EASIER Study: Switch ENF to RAL
Original article : Clin Infect Dis. 2009 Oct 15;49(8):1259-67 – N De Castro ; J Antimicrob Chemother. 2011 Sep;66(9):2099-106 – S Gallien ; J Infect Dis. 2013 Sep;208(6):892-7 – EF Silva
Last update : 28/03/2014

Dr Anton Pozniak
Chelsea and Westminster Hospital
London, UK

• From W24 data
  • In patients infected with multidrug-resistant HIV-1 receiving suppressive enfuvirtide-containing antiretroviral therapy, aswitch from enfuvirtide to RAL is:
    • Safe
    • Well-tolerated
    • And virologically non-inferior to the maintenance of ENF

Design :

Objective :

• Non inferiority in the proportion of patients with virologic failure at W24(Intent-to-treat analysis) ; upper limit of the 95% CI for the difference =10%, 80% power
• Virologic failure : confirmed HIV-1 RNA ≥ 400 c/mL, or a singleHIV-1 RNA ≥ 400 c/mL followed by treatment modification or last HIV-1 RNA ≥ 400 c/mL without confirmation

Baseline characteristics and patient disposition :

Outcome at week 24 :

Other endpoints

• Median CD4 increase
  • ENF: +15/mm3
  • RAL: +11/mm3
• No AIDS events
• No difference in the overall incidence of adverse reactions between both groups
• Higher incidence of grade 1 to 4 laboratory abnormalities in the RAL arm (p = 0.001)
• Median increases in triglycerides and total cholesterol were significantly higher in the RAL group

Grade 3 or 4 emerging adverse events or laboratory abnormalities :

At week 24

• ENF arm switched to RAL (deferred RAL), n = 84
• RAL arm continued on RAL (immediate RAL), n = 84

Week 48 analyses

• Primary : cumulative proportion of patients with confirmed HIV RNA ≥ 400 c/mL, or last HIV RNA ≥ 400 c/mL or treatment change after a single HIV RNA ≥ 400 c/mL (on-treatment and intent-to-treat analyses)
• Secondary
  • Proportion of patients with HIV RNA < 50 c/mL
  • Emergence of resistance in patients with virologic failure
  • Changes from baseline in CD4 cell counts
  • Proportion of patients with permanent discontinuation of RAL
  • Safety

Baseline GSS assessed on cumulative historical genotypes

• GSS ≥ 1 : 86% ; 0.5 : 11% ; 0 : 3% (n = 5)

• On-treatment analysis : 1 virologic failure (W8) in immediate arm ; baseline GSS = 0,no emergence of RAL-associated resistance mutations
• No significant changes in the median CD4 cell counts following RAL switch in either arm
• No significant changes between baseline and W48 in glucose levels or fasting lipidsin either arm

Grade 3 or 4 emerging adverse events or laboratory abnormalities In both arms between weeks 24 and 48 (N = 168) :

EASIER substudy: Inflammatory and coagulation biomarkers

• 164 patients, Immediate switch (n = 83) ; deferred switch (n = 81)
  
  
• Biomarkers
  • IL-6
  • hsCRP
  • D-dimer
    
    
• Primary objective : changes in IL-6, hsCRP and D-dimer plasma levels from baseline to W24 between the immediate and deferred arms
  • Log10 transformation of levels
  • Median changes from baseline assessed by 1-sample t tests
  • Comparison between arms used 2-sample t tests with no adjustment for baseline factors
    
    
• Similar analyses to compare changes from baseline to W48

 

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