Treatment simplification to once daily darunavir/ritonavir guided by the darunavir inhibitory quotient in heavily pretreated HIV-infected patients

Antivir Ther. 2010;15(2):219-25. doi: 10.3851/IMP1519.

Abstract

Background: We explored a treatment simplification strategy to darunavir/ritonavir 900/100 mg once daily guided by the darunavir virtual inhibitory quotient (vIQ) in patients receiving salvage therapy with darunavir/ritonavir 600/100 mg twice daily.

Methods: Open-label, randomized pilot study in HIV-infected patients on darunavir/ritonavir 600/100 mg twice daily (viral load <50 copies/ml; darunavir vIQ >2). Thirty patients were randomized to darunavir/ritonavir 900/100 mg once daily (once-daily group, n=15) or 600/100 mg twice daily (twice-daily group, n=15). Viral load, blood chemistry, and darunavir and ritonavir trough plasma concentrations (C(trough)) were determined up to 48 weeks. If the darunavir vIQ fell to <1.5, the dosage was switched to 600/100 mg twice daily. The primary end point was the percentage of 48-week treatment failure.

Results: Patients had taken a mean 11.6 (sd +/-3.9) antiretroviral regimens before darunavir/ritonavir administration. The proportion of patients without 48-week treatment failure was 86.7% in both groups. The median (interquartile range [IQR]) darunavir C(trough) decreased from 3.09 mg/l (IQR 2.43-3.93) at baseline to 1.60 mg/l (IQR 1.25-2.04) at week 48 (P=0.001) in the once-daily group. Three once-daily group patients switched to darunavir/ritonavir 600/100 mg twice daily. Fewer patients had triglyceride levels >200 mg/dl at week 48 in the once-daily group (20.0%) than in the twice-daily group (20.0% versus 57.1%; P=0.046).

Conclusions: Treatment simplification to darunavir/-ritonavir 900/100 mg once daily guided by the darunavir vIQ in treatment-experienced HIV-infected patients receiving darunavir/ritonavir 600/100 mg twice-daily seems to be safe enough to be tested in adequately powered clinical trials.

Trial registration: ClinicalTrials.gov NCT00611039.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents* / administration & dosage
  • Anti-HIV Agents* / therapeutic use
  • Darunavir
  • Drug Administration Schedule
  • Drug Resistance, Viral
  • Drug Therapy, Combination
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • HIV Protease Inhibitors* / administration & dosage
  • HIV Protease Inhibitors* / pharmacokinetics
  • HIV Protease Inhibitors* / pharmacology
  • HIV Protease Inhibitors* / therapeutic use
  • HIV-1 / drug effects*
  • Humans
  • Male
  • Pilot Projects
  • RNA, Viral / blood
  • Ritonavir* / administration & dosage
  • Ritonavir* / pharmacokinetics
  • Ritonavir* / pharmacology
  • Ritonavir* / therapeutic use
  • Salvage Therapy
  • Sulfonamides* / administration & dosage
  • Sulfonamides* / pharmacokinetics
  • Sulfonamides* / pharmacology
  • Sulfonamides* / therapeutic use
  • Treatment Outcome

Substances

  • Anti-HIV Agents
  • HIV Protease Inhibitors
  • RNA, Viral
  • Sulfonamides
  • Ritonavir
  • Darunavir

Associated data

  • ClinicalTrials.gov/NCT00611039