Switch studies in virologically suppressed patients

Switch to DRV/r 600/100 mg
LASA Study: switch to ATV/r 200/100 vs 300/100 mg QD
Original article : Bunupuradah T. Lancet HIV 2016;3:e343-50
Last update : 06/09/2016

Dr Anton Pozniak
Chelsea and Westminster Hospital
London, UK

  • ATV 200 mg and ritonavir 100 mg when combined with two NRTIs is non-inferior in terms of virological efficacy to ATV 300 mg and ritonavir 100 mg with two NRTIs in virologically suppressed Thai adults with HIV for use as second-line protease inhibitor-based ART
  • When switches from randomised treatment were imputed as failures, the low-dose group was superior to the standard-dose group because the standard-dose group was associated with increased treatment discontinuation because of adverse events
  • More patients in the low-dose ATV group than in the standard-dose group had trough concentrations lower than the recommended therapeutic concentration of 0.15 mg/L
  • Use of the low dose of ATV, with less toxicity than the standard dose, would benefit both patients and health-care systems (significant cost saving)

Design


* Randomisation stratified on site, treatment with TDF or with indinavir

Endpoints

  • Primary: proportion of patients with HIV RNA < 200 c/mL at W48 (ITT-E) ; non-inferiority if lower margin of the two-sided 95% CI for the difference = - 10%, 90% power
  • Secondary: proportion of patients with HIV RNA < 50 c/mL at W48, CD4 cell count changes, tolerability, adverse events, adherence, quality of life, cardiovascular risk, lipodystrophy

Baseline characteristics (ITT-e population) and patient disposition

Virological success at W48

ATV/r 200/100 (n = 273) ATV/r 300/100 (n = 277)

Genotype Resistance testing

  • Done in patients with protocol-defined virologic failure (confirmed HIV RNA ≥ 200 c/mL) and HIV RNA ≥ 1000 c/mL
    • ATV/r 200/100, N = 7 ; emergence of resistance in 1: I50L, V82A, L90M + resistance to all NRTIs
    • ATV/r 300/100, N = 1 ; no emergence of resistance

Study drug discontinuation

  • ATV/r 200/100, N = 7 (3%): 1 death, 2 virologic failures, 2 rashes, 1 jaundice, 1 pregnancy
  • ATV/r 300/100, N = 21 (8%): 1 death, 7 rashes, 6 jaundices, 1 pregnancy, 5 other reasons

Adverse events

  • Similar proportion in the 2 treatment groups

Mean change in laboratoty parameters from baseline to W48

Adverse events of special interest

Pharmacokinetic assessment

  • Serum samples collected at W12 and W24 for Ctrough measurements

 

 

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