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Switch to LPV/r monotherapy
OK04 Study: Switch LPV/r + 2NRTIs to LPV/r monotherapy
Original article : AIDS. 2008 Jan 11;22(2):F1-9 – F Pulido ; J Acquir Immune Defic Syndr. 2009 Jun 1;51(2):147-52 – JR Arribas
Last update : 28/03/2014

Dr Anton Pozniak
Chelsea and Westminster Hospital
London, UK

• From W48 data
  • In patients with virologic suppression for more than 6 months on LPV/r + 2 NRTIs, LPV/r monotherapy followed by re-introduction of the NRTIs as required is a therapeutic strategy as effective as continuing triple therapy: non inferiority of monotherapy was demonstrated
  • The vast majority of patients with loss of virologic suppressionon LPV/r monotherapy had no evidence of resistance mutations in the protease gene and were able to resupress and maintain virologic suppression after resumption of baseline NRTIs
• From W96 data
  • The 96 weeks results support the efficacy and safety of theLPV/r monotherapy strategy
  • Although episodes of low-level viremia were more frequent inthe monotherapy group, there was not an increased risk of resistance development and most of these patients could be virologically resupressed with addition of NRTIs
  • The toxicity of the LPV/r monotherapy regimen was lower than the toxicity of the triple regimen

Design :

Objective :

• Non inferiority of the monotherapy group in the proportion of patients with therapeutic failure at W48 (per-protocol analysis) ; upper limit of the 95% CIfor the difference = 12%, 80% power
• Therapeutic failure: 2 consecutive HIV-1 RNA > 500 c/mL (if no resistance at failure and successful viral suppression after reintroduction of 2 NRTIs, not considered as failure) ; change of randomised therapy ; treatment discontinuation ; loss to follow-up

Baseline characteristics and patient disposition :

Outcome at week 48 :

Response to treatment at week 48 :

• Therapeutic failures
  • 6 in the monotherapy group
    • 3 were lost to follow-up
    • 1 changed randomised therapy without loss of virologic suppression
    • 1 lost virologic suppression and developed PI resistance
    • 1 lost virologic suppression and failed to achieve suppression after reintroduction of NRTIs
  • 10 in the triple therapy arm
    • 4 were lost to follow-up
    • 3 had confirmed loss of virologic suppression
    • 3 discontinued randomised treatment due to adverse events
• Loss of virologic suppression at W48
  • 3 in the triple therapy group
  • 6 in the monotherapy group: of these 6, 4 resumed baseline NRTIs and regained virologic suppression, 1 had LPV/r resistance, and 1 did not achieve virologic suppression after resuming baseline NRTIs

Safety, Adverse events, Resistance, Adherence (W48) :

• Study drug-related adverse events of at least moderate severity
  • 3 in the triple therapy group (diarrhoea, N = 2, insomnia, N = 1), leading to treatment discontinuation
  • None in the monotherapy group (p = 0.08)
• No statistical significant changes from baseline in fasting total cholesterol, HDL cholesterol or triglycerides in both groups
• Genotypic analysis in patients with HIV-1 RNA > 500 c/mL
  • 3 in the triple therapy group:
    • PI resistance, N = 1 (mutations 54V, 63P, 71V and 82A)
    • NRTI resistance, N = 1
  • 11 in the monotherapy group:
    • PI resistance, N = 2 (mutations 10F and 46I in 1 ; mutations 54V, 77I and 82A in 1)
    • NRTI resistance, N = 1
• No difference in adherence between the 2 groups

Outcome at week 96 :

Point prevalence of discontinuations and virologic response through 96 weeks :

• After 2 years of follow-up, proportion of patients rebounding with isolates containing major PI mutations was 2% in each group

 

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