Head-to-head comparative trials for first line ART since 2006

Comparison of INSTI vs INSTI
QDMRK Study: raltegravir QD vs BID, with TDF/FTC
Original article : Lancet Infect Dis. 2011 Dec;11(12):907-15 - JJ Eron
Last update : 09/10/2014

Dr Anton Pozniak
Chelsea and Westminster Hospital
London, UK

  • At 48 weeks of treatment, RAL QD was not non-inferior to RAL BID, in combination with TDF/FTC
  • Virologic failure was more common with once-daily dosing especially in patients with baseline HIV RNA > 100 000 c/mL
  • More patients in the once-daily group than in the twice-daily group had resistance emergence to both RAL and FTC at the time of virological failure
  • Patients in the once-daily group with low pharmacokinetic values and high baseline viral loads were at particular risk of treatment failure
  • Despite a high response rate, RAL at 800 mg QD cannot be recommended in place of twice-daily dosing for first-line antiretroviral therapy

Design :


*Randomisation was stratified by baseline HIV RNA (< or > 100,000 c/mL) and viral hepatitis co-infection status

Objective :

  • Non inferiority of RAL QD: % HIV RNA < 50 c/mL by ITT, NC=F (lower margin of the 2-sided 95% CI for the difference = - 10%, 90% power)

Baseline characteristics and patient disposition :

Response to treatment at week 48 :









* Exclusion of discontinuations due to intolerability or reasons unrelated to treatment






* 95% CI for the difference = - 8.3 ; 2.7

Mean CD4/mm3 increase at W48 (observed-failure analysis):
+ 196 (RAL BID) vs + 210 (RAL QD)

Safety at W48 :

Virologic failure: definition

  • Non-response = never achieved 2 consecutive HIV RNA < 50 c/mL by week 24 or at time of premature study discontinuation
  • or rebound = after an initial response, confirmed HIV RNA ≥ 50 c/mL


* Genotyping was done only in patients with HIV RNA > 400 c/mL

2/2 (RAL BID) and 7/9 (RAL QD) patients who had emergence of RAL resistance
had baseline HIV RNA > 100 000 c/mL

Pharmacokinetic Data :

  • Trough raltegravir concentrations were more than six times higher with twice-daily dosing than they were with once-daily dosing
  • Although an association between trough RAL concentrations and efficacy was evident in the once-daily group, no clear threshold could be identified

 

 

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