Lopinavir/ritonavir (ABT-378/r)

Expert Opin Pharmacother. 2002 Mar;3(3):315-27. doi: 10.1517/14656566.3.3.315.


Despite major advances in HIV research, eradication of HIV from the body is not yet possible. However, current antiretroviral (ARV) therapy can achieve disease control via viral suppression below the limits of detection of currently available assays. This has led to a marked decline in morbidity and mortality associated with the development of opportunistic infections and malignancies. Since viral suppression appears to be the most achievable goal of current therapy, there arises a need for new and more potent ARV agents in order to maintain viral suppression. Many of the currently available protease inhibitors (PIs) have a high protein-binding ability, short plasma half-life [1] and pharmacokinetic interactions with food or other drugs [2]. This can result in sub-optimal plasma drug concentrations, which may allow the virus to break through and replicate, leading to the development of resistant mutants [1]. Lopinavir/ritonavir (LPV/r; Kaletra, Abbott Laboratories) is a new PI consisting of a co-formulation of lopinavir and low-dose ritonavir. The sub-therapeutic dose of ritonavir (a potent cytochrome P450 [CYP] 3A4 inhibitor) inhibits the metabolism of lopinavir, resulting in higher lopinavir concentrations than when lopinavir is administered alone [3]. This pharmacokinetic interaction is associated with a high lopinavir trough level:wild type median effective concentration (EC(50)) ratio and good general tolerability when compared with other currently licensed PIs [4]. The concept of pharmacokinetic enhancement - boosting - is not new as ritonavir has previously been utilised in this context with other PIs. The relationship between plasma and intracellular drug levels has yet to be clarified. What has been ascertained from pharmacokinetic studies thus far is the correlation between ARV trough plasma concentrations (C(min)) and virological outcome [5,6]. LPV/r exemplifies how the pharmacokinetic profile of a drug can be modified to attain sufficient C(min) to suppress pheno- and genotypically resistant viral strains, as well as provide a pharmacological barrier to the emergence of resistance [7]. LPV/r reduces pill-burden and aids compliance, as shown by encouraging results in the treatment of both ARV-naive and -experienced patients.

Publication types

  • Review

MeSH terms

  • Clinical Trials as Topic
  • Drug Interactions
  • Drug Therapy, Combination
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • HIV Protease Inhibitors / adverse effects
  • HIV Protease Inhibitors / pharmacokinetics
  • HIV Protease Inhibitors / pharmacology
  • HIV Protease Inhibitors / therapeutic use*
  • Humans
  • Lopinavir
  • Pyrimidinones / adverse effects
  • Pyrimidinones / pharmacokinetics
  • Pyrimidinones / pharmacology
  • Pyrimidinones / therapeutic use*


  • HIV Protease Inhibitors
  • Pyrimidinones
  • Lopinavir