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Synergistic inhibition of protease-inhibitor-resistant HIV type 1 by saquinavir in combination with atazanavir or lopinavir.

Authors
  • Dam, Elisabeth
  • Lebel-Binay, Sophie
  • Rochas, Séverine
  • Thibaut, Laurent
  • Faudon, Jean-Louis
  • Thomas, Claire-Marie
  • Essioux, Laurent
  • Hill, Andrew
  • Schutz, Malte
  • François Clavel
Type
Published Article
Journal
Diabetes Care
Publisher
American Diabetes Association
Publication Date
2007
Volume
12
Issue
3
Pages
371–380
Identifiers
PMID: 17591027
Source
USPC - SET - SVS
License
Unknown

Abstract

We hypothesize that differences between the PIs in intracellular protein-binding behaviour or inhibition of drug transporters (P glycoprotein, MDR1 and MDR2) could result in intracellular levels of saquinavir being increased by co-administration with lopinavir or atazanavir. The effect of this increase would be masked in cases involving viruses that were susceptible to atazanavir or lopinavir. In virus resistant to lopinavir or atazanavir but susceptible to saquinavir, the majority of the antiviral effect is due to saquinavir; thus even small increases in intracellular concentration could significantly increase virus inhibition. These results confirm that in vitro synergy can be observed between PIs and suggest that the degree of synergy observed might depend on the resistance profile of the virus.

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