Switch studies in virologically suppressed patients

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, a switch 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 single HIV-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 lipids in 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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