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Adherence to antiretroviral medications is usually expressed in terms of the proportion of doses taken. However, the timing of doses taken may also be an important dimension to overall adherence. Little is known about whether patients who mistime doses are also more likely to skip doses. Using data from the completed Adherence for Life randomized controlled trial, we created visual and statistical models to capture and analyze dose timing data collected longitudinally with electronic drug monitors (EDM). From scatter plots depicting dose time versus calendar date, we identified dominant patterns of dose taking and calculated key features [slope of line over calendar date; residual mean standard error (RMSE)]. Each was assessed for its ability to categorize subjects with 'sub-optimal' (<95 % of doses taken) using area under the receiver operating characteristic (AROC) curve analysis. Sixty eight subjects contributed EDM data, with ~300 to 400 observations/subject. While regression line slopes did not predict 'sub-optimal' adherence (AROC 0.51, 95 % CI 0.26-0.75), the variability in dose timing (RMSE) was strongly predictive (AROC 0.79, 95 % CI 0.62-0.97). Compared with the lowest quartile of RMSE (minimal dose time variability), each successive quartile roughly doubled the odds of 'sub-optimal' adherence (OR 2.1, 95 % CI 1.3-3.4). Patterns of dose timing and mistiming are strongly related to overall adherence behavior. Notably, individuals who skip doses are more likely to mistime doses, with the degree of risk positively correlated with the extent of dose timing variability. [ABSTRACT FROM AUTHOR]

Little is known about the importance of dose timing to successful antiretroviral therapy (ART). In a cohort comprised of Chinese HIV/AIDS patients, we measured adherence among subjects for 6 months using three methods in parallel: self-report using a visual analog scale (SR-VAS), pill count, and electronic drug monitors (EDM). We calculated two adherence metrics using the EDM data. The first metric used the proportion of doses taken; the second metric credited doses as adherent only if taken within a 1-h window of a pre-specified dose time (EDM ‘proportion taken within dose time’). Of the adherence measures, EDM had the strongest associations with viral suppression. Of the two EDM metrics, incorporating dose timing had a stronger association with viral suppression. We conclude that dose timing is also an important determinant of successful ART, and should be considered as an additional dimension to overall adherence. [ABSTRACT FROM AUTHOR]