title: A randomized clinical trial evaluating therapeutic drug monitoring (TDM) for protease inhibitor-based regimens in antiretroviral-experienced HIV-infected individuals: week 48 results of the A5146 study.
abstract: BACKGROUND
  We devised an open-label, randomized trial to evaluate whether therapeutic drug monitoring (TDM) of protease inhibitors (PIs) and dose escalation based upon a normalized inhibitory quotient (NIQ), which integrates PI trough concentration and drug resistance, could improve virologic outcome in PI-experienced patients with treatment failure. Secondary analyses through 48 weeks are presented.
  
  
  METHODS
  Eligible HIV-infected subjects with a screening viral load of ≥ 1000 copies/mL initiated a new PI-based regimen at entry and had NIQ performed at week 2. Subjects with an NIQ ≤1 were randomized at week 4 to a standard-of-care (SOC) arm or TDM arm featuring PI dose escalation.
  
  
  RESULTS
  One hundred and eighty-three subjects were randomized. There was no significant treatment difference in change from randomization to week 48 in HIV-1 RNA [ P = .13, median (25th, 75th percentile log10 copies/mL change): -0.03 (-0.74, 0.62) with TDM and 0.11 (-2.3, 0.82) with SOC]. In subgroup analysis, patients with ≥ 0.69 active PIs benefited from TDM compared to those with <0.69 active PIs ( P = .05).
  
  
  CONCLUSIONS
  While the TDM strategy of PI dose escalation did not improve virologic response at week 48 overall, in subgroup analysis, TDM favorably impacted virologic outcome in subjects taking PI-based regimens with moderate antiviral activity.
authors: Beth Israel Deaconess Medical Center, Boston, MA, USA. malbrech@bidmc.harvard.edu
authors: Mary
authors: M
authors: Albrecht
authors: A Lisa
authors: AL
authors: Mukherjee
authors: Camlin
authors: C
authors: Tierney
authors: Gene D
authors: GD
authors: Morse
authors: Carrie
authors: C
authors: Dykes
authors: Karin L
authors: KL
authors: Klingman
authors: Lisa M
authors: LM
authors: Demeter
mesh_terms: D000328:Adult; D018791:CD4 Lymphocyte Count; D016903:Drug Monitoring; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019562:Viral Load
chemical_list: D017320:HIV Protease Inhibitors