The extent of non-adherence in a large AIDS clinical trial using plasma dideoxynucleoside concentrations as a marker

AIDS. 1998 Dec 3;12(17):2305-11. doi: 10.1097/00002030-199817000-00012.


Objectives: To assess adherence to study medications in an AIDS clinical trial, to evaluate whether study participants adhered to only one component of a multidrug regimen ('differential adherence'), and to determine whether there was evidence of non-uniform adherence to study medications among treatment groups.

Setting: This was a substudy of AIDS Clinical Trials Group protocol 175, a large, double-blind, randomized study of monotherapy versus combination dideoxynucleoside therapy. Participants were required to adhere to a complex regimen of zidovudine, zalcitabine and didanosine, or their matching placebos.

Design: Between October 1992 and January 1994, study sites were selected at random, and a 1-week period was designated during which study participants attending routine clinic visits provided a blood sample and dosing history. Participants were not informed of the purpose of the substudy.

Measurements: Adherence was assessed using plasma drug concentrations and defined by the presence of detectable drug in a plasma sample obtained within a specified analysis window.

Results: Of 722 plasma samples analyzed, approximately 75% contained detectable concentrations of the assigned drugs and 5-14.5% contained no detectable drugs. Approximately 7 and 13% of samples from participants assigned to monotherapy arms contained non-prescribed dideoxynucleosides, and 14 and 19% assigned to combination therapies contained only one drug.

Conclusions: Various non-adherence behaviors were observed, including patterns of underdosing and taking non-prescribed drugs. Non-adherence was moderate but uniform amongst the treatment groups and may have contributed to a marginal reduction in the power of the primary intent-to-treat analysis to detect differences in efficacy amongst the assigned treatments.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acquired Immunodeficiency Syndrome / blood*
  • Acquired Immunodeficiency Syndrome / drug therapy
  • Adolescent
  • Adult
  • Aged
  • Anti-HIV Agents / administration & dosage
  • Anti-HIV Agents / blood*
  • Anti-HIV Agents / therapeutic use
  • Didanosine / administration & dosage
  • Didanosine / blood*
  • Didanosine / therapeutic use
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Humans
  • Male
  • Middle Aged
  • Patient Compliance*
  • Reverse Transcriptase Inhibitors / administration & dosage
  • Reverse Transcriptase Inhibitors / blood*
  • Reverse Transcriptase Inhibitors / therapeutic use
  • Zalcitabine / administration & dosage
  • Zalcitabine / blood*
  • Zalcitabine / therapeutic use
  • Zidovudine / administration & dosage
  • Zidovudine / blood*
  • Zidovudine / therapeutic use


  • Anti-HIV Agents
  • Reverse Transcriptase Inhibitors
  • Zidovudine
  • Zalcitabine
  • Didanosine