title: Therapeutic drug monitoring of nelfinavir and indinavir in treatment-naive HIV-1-infected individuals.
abstract: BACKGROUND
  Both virological failure and the toxicity of HIV protease inhibitors have been related to interindividual variability of plasma drug concentrations. Therapeutic drug monitoring (TDM) offers the possibility to detect patients with drug concentrations outside therapeutic ranges, who can subsequently benefit from dose modifications.
  
  
  METHODS
  ATHENA was a randomized controlled clinical trial. Subjects were randomly assigned to either a TDM group, in which the results of drug concentration measurements plus advice were reported to their treating physician, or to a control group for whom TDM results were not reported. This analysis refers to treatment-naive patients who started a regimen containing indinavir or nelfinavir before November 1999.
  
  
  RESULTS
  A total of 147 patients were randomly assigned: 92 to nelfinavir, 55 to indinavir. After one year of follow-up significantly fewer patients in the TDM group had discontinued nelfinavir or indinavir than in the control group: 17.4 versus 39.7%. This was mainly driven by a significantly lower rate of discontinuation because of virological failure in nelfinavir patients: 2.4% in the TDM group versus 17.6% in the control group, and by a non-significant difference in the rate of discontinuation because of toxicity in indinavir patients: 14.3% in the TDM group versus 29.6% in the control group. In a non-completer equals failure analysis of all randomized patients, the TDM group showed a significantly higher proportion of patients with a viral load below 500 copies after 12 months of treatment (78.2 versus 55.1%).
  
  
  CONCLUSIONS
  TDM of nelfinavir and indinavir in treatment-naive patients improves treatment response.
authors.affiliation: Department of Clinical Pharmacy, University Medical Centre, Nijmegen, the Netherlands. d.burger@akf.umcn.nl
authors.forename: David
authors.initials: D
authors.lastname: Burger
authors.forename: Patricia
authors.initials: P
authors.lastname: Hugen
authors.forename: Peter
authors.initials: P
authors.lastname: Reiss
authors.forename: Inge
authors.initials: I
authors.lastname: Gyssens
authors.forename: Margriet
authors.initials: M
authors.lastname: Schneider
authors.forename: Frank
authors.initials: F
authors.lastname: Kroon
authors.forename: Gerrit
authors.initials: G
authors.lastname: Schreij
authors.forename: Kees
authors.initials: K
authors.lastname: Brinkman
authors.forename: Clemens
authors.initials: C
authors.lastname: Richter
authors.forename: Jan
authors.initials: J
authors.lastname: Prins
authors.forename: Rob
authors.initials: R
authors.lastname: Aarnoutse
authors.forename: Joep
authors.initials: J
authors.lastname: Lange
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D004334:Drug Administration Schedule; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000097:blood / Q000627:therapeutic use*; D015497:HIV-1; D006801:Humans; D019469:Indinavir / Q000097:blood / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D019888:Nelfinavir / Q000097:blood / Q000627:therapeutic use*; D011446:Prospective Studies; D019562:Viral Load
chemical_list: D017320:HIV Protease Inhibitors; D019469:Indinavir; D019888:Nelfinavir