Switch studies in virologically suppressed patients

Switch to TDF/FTC/RPV
SPIRIT Study
Original article : AIDS. 2014 Jan 28;28(3):335-44 - FJ Jr Paella
Last update : 26/11/2014

Dr Anton Pozniak
Chelsea and Westminster Hospital
London, UK

  • Switching to the STR TDF/FTC/RPV from a PI/r regimen in virologically suppressed, HIV-1-infected participants maintained virologic suppression with a low risk of virologic failure, while improving total cholesterol, LDL-cholesterol, and triglycerides
    • Participants had been virologically suppressed on a PI/r regimen for at least 6 months prior to study entry and had no previous ART failure
    • Pretreatment HIV-1 RNA levels (while still ARV-naive) did not affect maintenance of viral suppression after switch to TDF/FTC/RPV
  • Historical K103 resistance mutation (probably transmitted) did not affect efficacy of switch to TDF/FTC/RPV in participants of the study

Design :


Objective :

  • Primary Endpoint : Non-inferiority in the proportion of patients with HIV-1 RNA < 50 c/mL at W24 (FDA snapshot analysis) ; upper limit of the 95% CI for the difference = 12%
  • Secondary Endpoints: Proportion of HIV1 RNA < 50 copies/mL at W48 ; Change in fasting lipid and CD4 cell count at W24 and W48 ; Safety and tolerability

Baseline characteristics and disposition :


ART at screening :


HIV RNA < 50 c/mL at W24 and W48 (ITT, snapshot) :


HIV RNA < 50 c/mL, ITT, M = excluded RPV = 99.7% vs PI/r = 94.7%

HIV RNA < 50 c/mL at W24 according to pre-ART HIV RNA :

Virologic failure

Among the 24 patients with the K103N mutation on historical genotype :

  • 18 in the immediate switch arm
    • All maintain HIV RNA < 50 c/mL at W24
    • 1 virologic failure at W48 (pre-existing mutations : K103N + V179I, emergence : M184V, E138K and V108V/I)
  • 6 in the delayed switch arm
    • 5 maintain HIV RNA < 50 c/mL at W48 (24 weeks after switch)
    • 1 without data at W48 (HIV RNA < 50 c/mL at last study visit)

Virologic failure on TDF/FTC/RPV, N = 7 (1.5%) :

  • 3 without emergence of resistance mutations
  • 4 with emergence of resistance mutations
    • K103N + L100I + M184I
    • M184I
    • E138E/K + M184M/V
    • E138K + V108V/I + M184V

Discontinuation for adverse event (W24) :

  • TDF/FTC/RPV, N = 6
    • tubulopathy, N = 1
    • neuro-psychiatric events, N = 4 (depression, headache, insomnia, psychiatric event)
  • 2 NRTI + PI/r, N = 0

GFR decrease significantly more important with RPV

Grade 3-4 Adverse events and laboratoratory abnormalities to W48 :

Mean change from baseline at W24 :

 

   

Back to Table of Contents

     
     
     
Copyright AEI 2017 | Links | Contact | Faculty and Disclosure | Terms of use aei