THE EXTENT OF NONADHERENCE IN A LARGE AIDS CLINICAL-TRIAL USING PLASMA DIDEOXYNUCLEOSIDE CONCENTRATIONS AS A MARKER

Objectives: To assess adherence to study medications in an AIDS clinic al trial, to evaluate whether study participants adhered to only one c omponent of a multidrug regimen ('differential adherence'), and to det ermine whether there was evidence of non-uniform adherence to study me dications 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. Pa rticipants were required to adhere to a complex regimen of zidovudine, zalcitabine and didanosine, or their matching placebos. Design: Betwe en October 1992 and January 1994, study sites were selected at random, and a 1-week period was designated during which study participants at tending routine clinic visits provided a blood sample and dosing histo ry. Participants were not informed of the put-pose of the substudy. Me asurements: Adherence was assessed using plasma drug concentrations an d defined by the presence of detectable drug in a plasma sample obtain ed 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. Approximate ly 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 underdos ing and taking non-prescribed drugs. Non-adherence was moderate but un iform amongst the treatment groups and may have contributed to a margi nal reduction in the power of the primary intent-to-treat analysis to detect differences in efficacy amongst the assigned treatments. (C) 19 98 Lippincott Williams & Wilkins.