In this cohort of children on ART we sought to determine the most practical and cost-effective method of measuring adherence in a RLS. MEMS was used as the reference method against which two subjective and two objective adherence assessments were compared. Of note, adherence as measured by MEMS (adjusted for dosing interval) in this study correlated with virologic suppression, which remained unchanged pre-and post-study.
Overall adherence by all measures was excellent: both subjective measures (VAS and 3DR) showed a median adherence of 100%. Overestimation of adherence is a common issue with subjective measures, which is why they are often not considered useful alone [31
]. Objective measures (PR and SR) however, had similarly high median adherence values in this study. All of the subjective and objective measures appeared to overestimate adherence when compared to MEMS.
The adherence rates in this young age group are similar to findings in older children [7
], except for PR adherence, which was higher in our cohort. It has recently been shown that caregiver motivation and knowledge of ART are important predictors of adherence [32
The fact that adherence rates were not lower in our very young cohort, where medication administration was further complicated by liquid formulations, suggests that motivational factors are of higher predictive importance than regimen complexity.
MEMS data showed that the timing of doses was often deviant from prescription—a finding that no other adherence measure could detect. Unfortunately, at an annual cost of $57 per patient including equipment and staff time, MEMS caps are not affordable in most RLS. While both subjective measures are easy to use and low cost at less than $0.40 per patients per annum per measure, neither correlated significantly with overall MEMS adherence. Only VAS showed significant correlation with timedMEMS—the correlation, however, was weak. Given the fact that VAS showed very little variance, this correlation’s relevance should be interpreted with caution. Similarly, the objective measures showed poor correlation with MEMS. Syrup returns were difficult to manage and required more staff time than simply calculating PR data.
For the objective measures, although PR has been shown to be a highly effective means of monitoring adherence in adults [18
], in our study PR overestimated adherence when compared to MEMS. This difference may be due to the different dispensing practices for syrups versus pills. For adults, exact numbers of pills can be counted and dispensed, whereas syrups can usually only be dispensed according to the manufacturers prepackaged volume. Since the dose of antiretroviral drugs changes with patient weight in children, no pharmacist is able to dispense an exact amount of syrup. The other objective measure, syrup returns, also overestimated adherence when compared to MEMS, possibly due to liquid spillage at dosing times. Another possibility is that of medication dumping—caregivers might deliberately empty medication containers before attending the clinic in order to appear adherent. Regardless, although PR is not as useful a tool in children as in adults, it is the more simple and cost effective measure if an objective method is to be used.
These results should be interpreted in light of several limitations. Due to limited financial and staff resources, we were only able to follow mother–child dyads for a short period of time, and it is possible that self-reported adherence was inflated (relative to MEMS adherence) over this short period. Overestimation of adherence by all measures but PR could also have occurred through the Hawthorne effect, due to the short monitoring period. It is also important to note that we measured only one antiretroviral drug of the regimen of three. Even though we included virologic data from subsequent visits after the adherence-monitoring period, the study cohort showed very little heterogeneity in their virologic response, and this limits the analyses. It is further noteworthy that the wider time frame during which specimen were collected could have influenced results. It is also important to note the limitations of our sample size—even though it is relatively large in comparison with other pediatric MEMS studies and with regards to our clinic population, its size is limiting in interpreting the significance of the detected associations and the overall statistical power of the data.
MEMS can over- or underestimate adherence, and even though we adjusted our data for these limitations, it cannot be guaranteed that all the caregiver reports that the adjustments were based on were correct.
Measuring adherence remains complex and elusive. The data here does highlight some areas where more intensive education should occur in the treatment support process: training with regard to amount and method of dosing syrups should be emphasized, as should timing of dosing. Although MEMS gave realistic adherence data in our study, no single adherence method is ideal. Our data suggest that PR and VAS would give an inexpensive assessment of objective and subjective adherence, but only VAS showed any correlation with MEMS usage. It is unfortunate that the expense of the best method renders it unavailable in RLS. As MEMS is repeatedly shown to be the best method of monitoring adherence, despite its limitations, perhaps more effort should be directed at the exploration of cheaper electronic alternatives for such RLS.