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

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.

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.

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.

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.

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.

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.