Protease inhibitor plasma concentrations in HIV antiretroviral therapy.

摘要: Since the introduction of HIV protease inhibitors in 1995, considerable progress has been made treatment HIV-infected patients. However, not without problems. Studies have demonstrated associations between inhibitor concentrations and efficacy some cases toxicity. As inter-individual intra-individual variations observed, it questioned to what extent this clinical implications with regard a consequence use concentration measurements optimise antiretroviral therapy (therapeutic drug monitoring--TDM) suggested. The objectives study, initiated 2000, were: establish method for simultaneous measurement available inhibitors; explore pharmacokinetics clinically relevant situations context; consider applicability TDM therapy. presented studies review demonstrate: 1) that is feasible measure plasma setting precision accuracy, are very stable during different circumstances ex vivo; 2) display limited long-term variation but variation; 3) morning evening case drug-drug interactions; 4) interactions can be unpredictable adverse also exploited increase or decrease dose; 5) increases enhance decreases reduce toxicity; 6) concentration-efficacy which established by others confirmed trials concentration-toxicity more difficult confirm. experiences understanding resulted new principles development better inhibitors. Most patients achieve several folds higher than minimum effective regimens used currently (2007). result become less receiving their first inhibitor. In experienced patients, harbouring varying degrees resistance/reduced susceptibility inhibitors, combination genotypic resistance testing, seems promising tool, prospective needed. certain conditions known associated (drug-drug interactions, gastrointestinal disease, pregnancy children) might benefit. no investigated these specifically randomised trials.