Quality assessment for therapeutic drug monitoring in AIDS Clinical Trials Group (ACTG 5146): a multicenter clinical trial. Academic Article uri icon



  • 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.


  • Wilkin, Timothy
  • DiFrancesco, Robin
  • Rosenkranz, Susan
  • Mukherjee, A Lisa
  • Demeter, Lisa M
  • Jiang, Hongyu
  • DiCenzo, Robert
  • Dykes, Carrie
  • Rinehart, Alex
  • Albrecht, Mary
  • Morse, Gene D

publication date

  • August 1, 2010



  • Acquired Immunodeficiency Syndrome
  • Anti-HIV Agents
  • Antiretroviral Therapy, Highly Active
  • Drug Monitoring


PubMed Central ID

  • PMC2936454

Scopus Document Identifier

  • 77955171884

Digital Object Identifier (DOI)

  • 10.1097/FTD.0b013e3181e4427a

PubMed ID

  • 20592644

Additional Document Info


  • 32


  • 4