Switch studies in virologically suppressed patients

Switch to DRV/r monotherapy
MONET Study: Switch PI or NNRTI to DRV/r qd monotherapy
Original article : AIDS. 2010 Jan 16;24(2):223-30 – JR Arribas ; Rieger A, et al. AIDS 2010; Abs. THLBB209 ; HIV Med. 2012 Aug;13(7):398-405 – JR Arribas
Dernière mise à jour : 28/03/2014
Last update : 28/03/2014

Dr Anton Pozniak
Chelsea and Westminster Hospital
London, UK

  • From W48 data
    • In patients with virologic suppression on standard triple therapy (2 NRTIs + 1 NNRTI or 1 PI), once-daily DRV/r monotherapy has shown non inferior HIV RNA suppression at week 48 compared with a standard therapy of 2 NRTIs + once-daily DRV/r
    • A switch to once-daily DRV/r monotherapy can be considered in patients who have HIV RNA < 50 c/mL for more than 6 months on other treatments and no history of virologic failure, but wish to avoid toxicities related to other ARVs

Design :

Objective :

  • Non inferiority in the proportion of patients with HIV-1 RNA < 50 c/mL at W48 (per-protocol analysis, switch= failure, TLOVR algorithm) ; lower limit of the 95% CI for the difference= - 12%, 80% power

Baseline characteristics and patient disposition :

  • At baseline, 13 patients had HIV-1 RNA levels > 50 c/mL (9 in the monotherapy arm and 4 in the triple therapy arm) despite having results < 50 c/ml at screening

Results: W48 outcome :

  • Non inferiority of DRV/r monotherapy

Outcomes of confirmed HIV RNA elevations :

Outcomes of discontinuations from the trial :

Other endpoints :

  • In multivariate analysis, hepatitis C co-infection was a significant predictor of confirmed HIV RNA elevations (p < 0.01)
  • Resistance data: Genotype was available for 35/61 patients with HIV RNA > 50 c/mL (22 in the monotherapy group and 13 in the triple therapy group)
    • Resistance mutations to PI in 1 one patient in each arm, with no phenotypic resistance to DRV. HIV-1 RNA returned to < 50 c/mL without changing therapy in both patients
  • Most common grade 2 to 4 adverse events (AE) were gastrointestinal
  • Serious AE were seen in 9 patients in each group
  • Discontinuation for AE by W48 occurred in 8 patients in the monotherapy group and 3 in the triple therapy group
  • Grade 1 to 4 nervous system AE were seen in 16% of patients in each group, and Grade 1 to 4 psychiatric AE in 9% of patients in each group
  • There were more haematological abnormalities in the triple therapy arm, related to zidovudine

Results: W96 outcome :

  • Monotherapy is not noninferior with switch = failure analysis at W96
    • Δ -5.8% (95% CI: -16.0% to +4.4%)
  • If resuppression with intensification included as success, then monotherapy is noninferior at W96
    • Δ +1.4% (95% CI: -5.5% to +8.3%)

HIV-1 RNA < 50 c/mL at W144 (ITT-TLOVR) :


* Change in ARV

  • 2 consecutive HIV-1 RNA > 50 c/mL:
    • DRV/r monotherapy, N = 21
    • DRV/r + 2 NRTI, N = 13
    • 18/21 and 10/13 had HIV-1 RNA < 50 c/mL at W144
  • Level of HIV-1 RNA at baseline and HCV co-infection were significantly associated with transient viremia during the 144 weeks (p < 0.05)
  • Resistance emergence to PI (IAS-USA): 1 in each arm, both before W24

 

   

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