Repeated measures analyses of dose timing of antiretroviral medication and its relationship to HIV virologic outcomes.

Medication adherence is a critical predictor of the effectiveness of antiretroviral medications in the treatment of HIV/AIDS. Studies of adherence, however, have focused primarily on the per cent of prescribed doses taken (per cent adherence). In the Adherence and Efficacy of Protease Inhibitor Therapy study, we collected detailed adherence data including dose timing information as well as data regarding patients' virologic responses. For 48 weeks, adherence data and virologic outcomes were collected every 4 weeks, and demographics and other measures were collected at baseline and at weeks 8, 24, and 48. We constructed eight different dose timing error (DTE) measures and evaluated their associations with virologic outcomes using longitudinal analyses. Repeated measures mixed effect models were fitted to evaluate the predicting power of each of the DTE measures. Among 52 036 electronically measured doses obtained from 122 patients, DTE measures significantly predicted virologic outcomes. Of the eight different DTE measures, the six DTE measures were significantly predictive of virologic outcomes even after controlling for per cent adherence. In conclusion, we identified several measures of DTE that explain HIV virologic outcomes not captured by traditional adherence measures. Investigations of adherence to antiretrovirals would benefit from measuring not only per cent adherence but dose timing adherence.