Our finding that pillbox organizer use improved adherence is supported by the results of a recent trial in which elderly patients were randomized to receive their medications in time-specific blister packs, together with pharmacy-based follow-up [18
]. The study found a significant improvement in adherence among the subjects who received the combined intervention; however, it was not possible to determine to what extent the improved adherence was attributable to the use of the medication organizers, as opposed to pharmacy follow-up. The results presented here suggest that medication organizers make an important independent contribution to improved adherence.
Prior findings on the effect of medication organizer use on adherence have been summarized in a systematic review [19
]. The authors reviewed the results of 12 randomized trials and concluded that there was a trend towards improved adherence among patients who used a medication organizer. One-half of the trials included in this review showed a statistically significant effect of medication organizer use only. However, as the authors point out, the majority of the studies reviewed had small sample sizes and short periods of follow-up, and thus would not have been able to detect a small-to-moderate–sized effect. Interpretation of the results was further complicated by the diversity of outcome assessments and methodologic heterogeneity. For example, a trial by Huang et al. [20
] that did not conclude a benefit from organizer use may have been limited in its ability to detect such an effect, because it relied on clinic-based pill counts to measure adherence and was based on a small number of volunteers who reported very high adherence levels in both treatment groups. Two additional trials, not included in the systematic review, were similarly limited in their ability to detect differences in adherence because of their small sample size [21
] and the inherent imprecision of self-reported adherence [21
] or clinic-based pill count adherence measures [22
]. Finally, a single observational study also found a trend towards better adherence among individuals who used adherence aids, such as reminder devices or pillbox organizers [23
Our observations suggest that pillbox organizer use is associated with a 4%–5% higher adherence in a predominantly urban poor, HIV-positive population receiving antiretroviral therapy. This estimate was reached by 3 separate statistical approaches controlling for common variables that may confound the effect of pillbox organizer use on adherence. A 4% improvement in adherence is associated with a difference of 0.12 log10
copies/mL in viral load [2
] and an 11% reduction in the risk of progression to clinical AIDS [8
]. More-intensive adherence interventions have been associated with a 10%–15% improvement in objectively measured adherence [24
]. Using the Johns Hopkins cohort, Goldie et al. [29
] estimated that a $100 per month intervention that improved adherence by 10% was associated with a cost-effectiveness ratio of <$50,000 per quality-adjusted life-year. In their analysis, they found that a 14.5% increase in the rate of viral suppression corresponded to a reduction of ~20% in the monthly treatment failure rate. shows estimates of the cost per quality-adjusted life-year for a range of adherence interventions, with differing monthly costs and differing effectiveness (in terms of an improved rate of viral suppression). To the extent that the REACH cohort and Johns Hopkins cohort are comparable urban poor, HIV-positive populations, we estimate that pillbox organizer use, at $5 per month, should be associated with a cost of ~$19,000 per quality-adjusted life-year ().
Figure 1 Relationship between cost of adherence intervention, percentage improvement in viral suppression, and cost per quality-adjusted life-year (QUALY) gained, based on the Johns Hopkins cohort .
There are a number of limitations to our study. First, we cannot exclude the possibility that intensive adherence monitoring changed adherence. However, both pillbox users and nonusers received unannounced pill counts, which, therefore, should not be a source of bias in our estimated effect of pillbox use. In addition, the control group (consisting of individuals who were not using pillbox organizers) received electronic pill cap monitoring, which may have altered adherence. Studies to date, however, have been unable to detect an effect of intensive adherence monitoring on adherence behavior [30
]. If electronic monitoring in the control group did alter adherence, it would most likely increase adherence in the control group and bias our results to an underestimate of the effect of pillbox organizers on adherence. Second, as in any observational study, we cannot exclude the possibility of unmeasured confounding. However, we controlled for major known confounders of intervention effects on adherence and viral load, using sophisticated data-adaptive regression techniques and cross-validation. Finally, most of the patients in this study received twice-daily regimens with several pills per dose. It is unclear whether pillbox organizers would have the same effect on the simpler regimens that are in use today.
Our study also had several strengths. Data were drawn from a well-studied cohort with very high retention rates and well-characterized, objective adherence measures. Use of unannounced pill counts helped protect against overestimation of adherence as a result of “pill dumping,” and the effect of pillbox organizers on viral load was also assessed. Finally, state-of-the-art data analyses and the use of alternative methods to control for confounding improved the robustness of the findings.
The urban poor and recreational drug users were highly represented in the target population of this study. Although this population has often been regarded as having difficulty with adherence, adherence problems are by no means limited to patients with low socioeconomic status. Therefore, the findings of this study may have broad applications for more-affluent patient populations.
In summary, we found that pillbox organizers are associated with improved adherence to HIV antiretroviral therapy and improved viral suppression in a diverse population with a wide distribution of adherence. These improvements are likely to be associated with favorable cost per quality-adjusted life-year. The successful treatment of HIV infection is similar to that of other chronic diseases, such as diabetes mellitus and hypertension; to prevent disease progression, individuals must maintain high levels of medication adherence to complex therapies, often in the absence of symptoms, for the duration of their lifetimes. Additional work is needed to demonstrate whether pillbox organizers similarly improve adherence to medical therapies other than antiretroviral drugs. However, given the simplicity and low cost of the intervention, clinicians should consider including pillbox organizers in their routine treatment of chronic disease.