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In Reply We thank Dr de Bruin for his thoughtful comments. First, we agree that nonuse of electronic monitors (EMs) despite taking the medication can introduce bias.1 In Dr de Bruin’s scenario, nonuse of EMs would be more common in controls, biasing adherence results in favor of the intervention. We attempted to avoid this bias at each visit by emphasizing the importance of using the EMs, querying about their use and reiterating their importance if participants reported nonuse. Fewer than 5% of reports from all visits included taking unmonitored doses more than weekly. Of course, these self-reports themselves may have been biased. Yet, importantly, differential monitor use would have had no effect on virologic differences between the study arms—only the differences in adherence would have been affected. We therefore agree with Dr de Bruin that demonstrating that adherence mediated the effect on virologic outcome would further support the trial results,2 and we have performed the additional analysis he suggested. The association between our intervention and virologic suppression decreased from 1.48 (95% CI, 0.94-2.31) in unadjusted models to 1.04 (95% CI, 0.64-1.70) in models adjusted for EM-measured adherence. Moreover, for every 1–percentage-point increase in EM-measured adherence, the probability of undetectable viral load increased by 2.8% (95% CI, 2.0%-3.6%) (P < .001). We interpret these findings to mean that the EMs captured important true adherence differences, and the adherence improvement increased virologic response rates.
Gross R, Bellamy SL, Strom BL. Does Managed Problem Solving Work and in What Setting?—Reply. JAMA Intern Med. 2013;173(15):1475-1476. doi:10.1001/jamainternmed.2013.7782