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Characterizing patterns of drugtaking behavior with a multiple drug regimen in an AIDS clinical trial

Kastrissios, Helen1,4; Suárez, José-Ramón1,5; Katzenstein, David2; Girard, Pascal6,3; Sheiner, Lewis B.3; Blaschke, Terrence F.1,7

Article

Objective: To characterize drug-taking behavior using continuous electronic monitoring in an AIDS clinical trial.

Setting: This was a substudy of AIDS Clinical Trials Group (ACTG) protocol 175, a phase II/III study of dideoxynucleoside monotherapy versus combination therapy in asymptomatic HIV-positive subjects. Participants were required to comply with regimens containing zidovudine, zalcitabine and didanosine, or matching placebos; the total daily pill count was 16.

Design: For participants at two ACTG 175 sites, electronic devices were used to monitor drug-taking behavior of all study medications over a period of approximately 90 days.

Measurements: Four indices of drug-taking behavior were calculated and their distributions and relationship to the prescribed regimen were examined.

Results: Data from 41 subjects were analyzed. Of the prescribed doses of zidovudine, zalcitabine and didanosine, 88, 84 and 82%, respectively, were taken. Of these, 55, 66 and 79%, respectively, were taken at the prescribed dosing frequency. The median percentage of days on which participants failed to take any of the doses was 2–5%. There was a trend towards lower adherence in the combination therapy arms compared with those assigned to receive monotherapy. In this analysis, older patients demonstrated better adherence, although patient characteristics, in general, were poorly predictive of adherence.

Conclusion: Drug-taking behavior for all three active study medications differed from that prescribed. One result of this erratic adherence was that study participants sustained little antiretroviral effect during more than 25% of the monitoring period.

1Division of Clinical Pharmacology, Stanford University School of Medicine, Stanford, USA

2Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine, Stanford, USA

3Department of Laboratory Medicine, University of California, San Francisco, California, USA

4Department of Pharmaceutics and Pharmacodynamics, University of Illinois at Chicago, Chicago, Illinois, USA

5Global Clinical Pharmacology, Hoechst Marion Roussel, Inc., Bridgewater, New Jersey, USA

6Clinical Pharmacology Unit, Hôpital Cardiologique, Lyon, France.

7Requests for reprints to: Dr Terrence F. Blaschke, Division of Clinical Pharmacology, Rm S-009, Stanford University School of Medicine, Stanford, CA 94305-5130, USA.

Note: Preliminary data were presented in part at the 96th Annual Meeting of the American Society of Clinical Pharmacology, San Diego, March 1995 and at the 18th AIDS Clinical Trial Group Meeting, Washington, DC, July 1994.

Sponsorship: Supported by NIH NIAID grant AI27666; J-R.S. was supported by a Merck Sharp & Dohme International Fellowship in Clinical Pharmacology; P.G. was an INSERM Research Fellow.

Date of receipt: 19 May 1998; revised: 24 August 1998; accepted: 1 September 1998.

© 1998 Lippincott Williams & Wilkins, Inc.