title: A randomized controlled trial of therapeutic drug monitoring in treatment-naive and -experienced HIV-1-infected patients.
abstract: OBJECTIVE
  To improve the utility of therapeutic drug monitoring (TDM) by defining the proportion of patients with and predictors of above or below target protease inhibitor (PI) or nonnucleoside reverse transcriptase inhibitor (NNRTI) concentrations.
  
  
  METHODS
  This 48-week, multicenter, open-label clinical trial randomized patients to TDM versus standard of care (SOC). Serial pharmacokinetics, including a week-2 3-sample sparse collection, and expert committee TDM recommendations were given to TDM-arm patients' providers.
  
  
  RESULTS
  Seventy-four (39%) of 190 patients had week-2 concentrations outside of targets and 122 (64%) of 190 had nontarget exposure at least once over 48 weeks. Providers accepted 75% of TDM recommendations. Among patients with below-target concentrations, more TDM-arm than SOC-arm patients achieved targets (65% vs. 45%; P = 0.09). Increased body weight and efavirenz or lopinavir/ritonavir use were significant predictors of nontarget concentrations. Patients at target and patients who achieved targets after TDM-directed dose modifications trended toward greater viral load reductions at week 48 than patients with below-target exposures (HIV RNA reductions: 2.4, 2.3, and 1.9 log10 copies/mL, respectively; P = 0.09).
  
  
  CONCLUSIONS
  Most patients had nontarget PI and/or NNRTI concentrations over 48 weeks. TDM recommendations were well accepted and improved exposure. Patients below TDM targets trended toward worse virologic response.
authors.affiliation: University of California, San Diego, San Diego, CA 92013, USA. brookie@ucsd.edu
authors.forename: Brookie M
authors.initials: BM
authors.lastname: Best
authors.forename: Miguel
authors.initials: M
authors.lastname: Goicoechea
authors.forename: Mallory D
authors.initials: MD
authors.lastname: Witt
authors.forename: Loren
authors.initials: L
authors.lastname: Miller
authors.forename: Eric S
authors.initials: ES
authors.lastname: Daar
authors.forename: Catherine
authors.initials: C
authors.lastname: Diamond
authors.forename: Jeremiah G
authors.initials: JG
authors.lastname: Tilles
authors.forename: Carol A
authors.initials: CA
authors.lastname: Kemper
authors.forename: Robert
authors.initials: R
authors.lastname: Larsen
authors.forename: Diane T
authors.initials: DT
authors.lastname: Holland
authors.forename: Shelly
authors.initials: S
authors.lastname: Sun
authors.forename: Sonia
authors.initials: S
authors.lastname: Jain
authors.forename: Glenn
authors.initials: G
authors.lastname: Wagner
authors.forename: Edmund V
authors.initials: EV
authors.lastname: Capparelli
authors.forename: J Allen
authors.initials: JA
authors.lastname: McCutchan
authors.forename: Richard H
authors.initials: RH
authors.lastname: Haubrich
mesh_terms: D000328:Adult; D000465:Algorithms; D019380:Anti-HIV Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D015992:Body Mass Index; D018791:CD4 Lymphocyte Count; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics; D015497:HIV-1; D006801:Humans; D008297:Male; D008875:Middle Aged; D044469:Racial Groups; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics