title: A randomized trial of therapeutic drug monitoring of protease inhibitors in antiretroviral-experienced, HIV-1-infected patients.
abstract: OBJECTIVE
  Whether therapeutic drug monitoring of protease inhibitors improves outcomes in HIV-infected patients is controversial. We evaluated this strategy in a randomized, open-label clinical trial, using a normalized inhibitory quotient (NIQ), which incorporates drug exposure and viral drug resistance. NIQs < or = 1 may predict poor outcome and identify patients who could benefit from dose escalation.
  
  
  METHODS
  Eligible patients had a viral load > or =1000 copies/ml on a failing regimen, and began a new protease inhibitor containing regimen at entry. All FDA-approved protease inhibitors available during the study recruitment (June 2002-May 2006) were allowed. One hundred and eighty-three participants with NIQ < or = 1, on the basis of their week 2 protease inhibitor trough concentration and pre-entry drug resistance test, were randomized at week 4 to standard of care (SOC) or protease inhibitor dose escalation (TDM). The primary endpoint was change in log10 plasma HIV-1 RNA concentration from randomization to 20 weeks later.
  
  
  RESULTS
  Ninety-one patients were randomized to SOC and 92 to TDM. NIQs increased more in the TDM arm compared to SOC (+69 versus +25%, P = 0.01). Despite this, TDM and SOC arms showed no difference in outcome (+0.09 versus +0.02 log10, P = 0.17). In retrospective subgroup analyses, patients with less HIV resistance to their protease inhibitors benefited from TDM (P = 0.002), as did black and Hispanic patients (P = 0.035 and 0.05, respectively). Differences between black and white patients persisted when accounting for protease inhibitor susceptibility.
  
  
  CONCLUSIONS
  There was no overall benefit of TDM. In post hoc subgroup analyses, TDM appeared beneficial in black and Hispanic patients, and in patients whose virus retained some susceptibility to the protease inhibitors in their regimen.
authors.affiliation: University of Rochester School of Medicine and Dentistry, New York, USA. lisa_demeter@urmc.rochester.edu
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Demeter
authors.forename: Hongyu
authors.initials: H
authors.lastname: Jiang
authors.forename: A Lisa
authors.initials: AL
authors.lastname: Mukherjee
authors.forename: Gene D
authors.initials: GD
authors.lastname: Morse
authors.forename: Robin
authors.initials: R
authors.lastname: DiFrancesco
authors.forename: Robert
authors.initials: R
authors.lastname: DiCenzo
authors.forename: Carrie
authors.initials: C
authors.lastname: Dykes
authors.forename: Prakash
authors.initials: P
authors.lastname: Sista
authors.forename: Lee
authors.initials: L
authors.lastname: Bacheler
authors.forename: Karin
authors.initials: K
authors.lastname: Klingman
authors.forename: Alex
authors.initials: A
authors.lastname: Rinehart
authors.forename: Mary
authors.initials: M
authors.lastname: Albrecht
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D004334:Drug Administration Schedule; D016903:Drug Monitoring / Q000379:methods*; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D017320:HIV Protease Inhibitors; D012367:RNA, Viral