Quality Assessment for Therapeutic Drug Monitoring in AIDS Clinical Trials Group (ACTG 5146): A Multicenter Clinical Trial

Ther Drug Monit. 2010 Aug;32(4):458-66. doi: 10.1097/FTD.0b013e3181e4427a.


In a randomized trial, AIDS Clinical Trials Group (ACTG) protocol 5146 (A5146) investigated the use of therapeutic drug monitoring (TDM) to adjust doses of HIV-1 protease inhibitors (PIs) in patients with prior virologic failure on PI-based therapy who were starting a new PI-based regimen. The overall percentage of "PI trough repeats" such as rescheduled visits or redrawn PI trough specimens increased from 2% to 5% to 10% as the process progressed from the clinical sites, the pharmacology specialty laboratory, and the study team, respectively. Cumulatively, this represents a 17% rate of failure to obtain adequate PI trough sample. While targeting a turnaround of 7 days or less from sample receipt to a drug concentration report, 12% of the received specimens required a longer period to report concentrations. The implementation of dosing changes in the TDM arm were achieved within 7 days or less for 56% of the dose change events and within 14 days or less for 77% of dose change events. This quality assurance analysis provides a valuable summary of the specific points in the TDM process that could be improved during a multicenter clinical trial including: 1) shortening the timeline of sample shipment from clinical site to the laboratory; 2) performing the collection of PI trough specimen within the targeted sampling window by careful monitoring of the last dose times and collection times by the clinicians; 3) increasing patient adherence counseling to reduce the number of samples that are redrawn due to suspecting inconsistent adherence; and 4) decreasing the time to successful TDM-based dose adjustment. The application of some of these findings may also be relevant to single-center studies or clinical TDM programs within a hospital.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acquired Immunodeficiency Syndrome / drug therapy*
  • Anti-HIV Agents / blood
  • Anti-HIV Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active / methods*
  • Calibration
  • Drug Monitoring / standards*
  • HIV Protease Inhibitors / blood
  • HIV Protease Inhibitors / therapeutic use
  • HIV-1
  • Humans
  • Laboratories / standards
  • Quality Control
  • Specimen Handling / standards
  • Treatment Outcome


  • Anti-HIV Agents
  • HIV Protease Inhibitors

Grant support