A review of low-dose ritonavir in protease inhibitor combination therapy

Clin Infect Dis. 2003 Jun 15;36(12):1585-92. doi: 10.1086/375233. Epub 2003 Jun 5.


The pharmacokinetics of protease inhibitors center around the microsomal enzyme cytochrome P-450 3A4. As a potent inhibitor of this enzyme, ritonavir can increase the bioavailability and half-life of coadministered protease inhibitors. Evidence suggests that increased exposure to protease inhibitors is clinically relevant. Antiretroviral treatment with low-dose ritonavir-boosted lopinavir, indinavir, and saquinavir has durable virological activity and shows impressive immune reconstitution. Although tolerable in most cases, gastrointestinal side effects, hepatotoxicity, and blood lipid abnormalities remain relevant issues. Additional study will elucidate the advantages and disadvantages of twice-daily, low-dose ritonavir-boosted regimens and determine whether once-daily regimens based on this principle will have a lasting role in clinical practice.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antiretroviral Therapy, Highly Active
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 Enzyme System / drug effects
  • Cytochrome P-450 Enzyme System / metabolism
  • Drug Resistance, Viral
  • Drug Therapy, Combination
  • HIV Infections / drug therapy*
  • HIV Protease Inhibitors / administration & dosage
  • HIV Protease Inhibitors / therapeutic use*
  • Humans
  • Indinavir / therapeutic use
  • Ritonavir / administration & dosage
  • Ritonavir / therapeutic use*
  • Saquinavir / administration & dosage
  • Saquinavir / therapeutic use


  • HIV Protease Inhibitors
  • Indinavir
  • Cytochrome P-450 Enzyme System
  • CYP3A protein, human
  • Cytochrome P-450 CYP3A
  • Saquinavir
  • Ritonavir