Pharmacokinetics, protein-binding-adjusted inhibitory quotients for atazanavir/ritonavir 300/100 mg in treatment-naïve HIV-infected patients

HIV Med. 2010 Nov;11(10):666-9. doi: 10.1111/j.1468-1293.2010.00839.x.

Abstract

Objectives: Studies have shown the importance of having a high protein-binding-adjusted inhibitory quotient (IQ) for protease inhibitors (PIs) boosted with ritonavir. The objective of this study was to explore the virological response when combination atazanavir/ritonavir was administered to treatment-naı¨ve patients.

Methods: Protein-binding-adjusted IQs were calculated in 100 treatment-naı¨ve patients initiating therapy with atazanavir 300 mg/ritonavir 100 mg plus two nucleoside reverse transcriptase inhibitors.

Results: The median atazanavir trough level was 635 ng/mL [interquartile range (IQR) 342-1000] and the median atazanavir protein-binding-adjusted IQ was 45 (IQR 24-71). Eighty-four per cent of patients had a successful virological response, and those who failed did not develop resistance. The IQ for boosted atazanavir is high, resulting in rare treatment failure without resistance mutations.

Conclusions: This study showed that the protein-binding-adjusted IQ of atazanavir is close to those measured for lopinavir and darunavir used once daily in first-line treatment. Finally the selection of resistance in the case of virological failure (plasma viral load 4400 HIV-1 RNA copies/mL) to atazanavir/ritonavir used in first-line therapy seems uncommon, as it is for all boosted PIs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Atazanavir Sulfate
  • Blood Proteins / metabolism
  • Drug Resistance, Multiple, Viral
  • Drug Therapy, Combination
  • Female
  • HIV Infections / drug therapy
  • HIV Infections / metabolism*
  • HIV Protease Inhibitors / administration & dosage
  • HIV Protease Inhibitors / pharmacokinetics*
  • HIV-1 / drug effects
  • HIV-1 / genetics
  • Humans
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Oligopeptides / administration & dosage
  • Oligopeptides / pharmacokinetics*
  • Protein Binding
  • Pyridines / administration & dosage
  • Pyridines / pharmacokinetics*
  • Ritonavir / administration & dosage
  • Ritonavir / pharmacokinetics*
  • Treatment Outcome
  • Viral Load
  • Young Adult

Substances

  • Blood Proteins
  • HIV Protease Inhibitors
  • Oligopeptides
  • Pyridines
  • Atazanavir Sulfate
  • Ritonavir