PAMs are ideally suited to monitoring adherence because they are objective and can be easily derived from data routinely collected for other purposes, such as clinical care, medication billing, fulfillment of legal requirements, or drug supply management. Importantly, PAMs may overestimate actual pill taking if individuals discard or share pills and, therefore, estimate maximum possible adherence. In addition, PAMs do not provide information on patterns of nonadherence known to be associated with the development of resistance to NNRTIs [51
Despite their limitations, in settings in which frequent routine viral load monitoring is not available, PAMs can play an important role in monitoring individual and population-level adherence to ART. Although prospective studies of adherence interventions and viral load testing targeted at patients with lower levels of adherence, as determined by PAMs, have not been reported, findings from 2 studies are optimistic [17
]. In a study conducted in sub-Saharan Africa, PAMs were superior to CD4 cell count criteria in predicting virological failure, and when PAMs were performed before determinations of viral load and CD4 cell count, PAMs were as accurate as CD4 cell count changes in predicting virological failure. These results support the use of PAMs for potential identification of patients at risk of future virological failure [17
]. In a second study, which was from Canada, analysis of repeated measures of adherence, which account for changes in adherence over time, predicted future viral rebound [36
], suggesting that routine surveillance of patient adherence with PAMs can be used to alert clinicians to possible future virological failure.
Use of PAMs to monitor adherence requires the following minimum data: ART regimen dispensed, date of dispensing, and number of days of ART dispensed. Selection of a PAM will depend on available resources at a site or in a program, as well as a local assessment of the strengths and limitations of different PAMs. MPR estimates are the most studied and incorporate time in the denominator (); thus, patients need to return to the dispensary before their medication finishes if taken as prescribed, to be considered 100% adherent. PC and PPU measures that do not incorporate time in the denominator () may overestimate adherence, because patients may use all dispensed ART but do so over longer periods than intended. PC measures are limited by the increased resources required to routinely count and record remnant pills at each clinic or pharmacy visit. In addition, if patients do not bring all remnant pills for counting or share or lose pills, the rate of adherence will be overestimated. Although PC measures may provide a more accurate assessment of adherence by accounting for unused ART, to our knowledge, no data comparing PC to non-PC PAMs are available. PPU measures are the least studied PAM. Unlike MPR and PC measures, PPU estimates are dichotomous and, therefore, do not provide a range of adherence, limiting their ability to identify individuals in need of increased adherence support.
In the absence of data suggesting an advantage of PC over non-PC measures, and considering the extra resources required to count remnant pills, we do not suggest using PC measures. Furthermore, measures incorporating the number of days for which ART was prescribed in their definition, such as MPR and some PPU, measures are likely to be the most informative. Available data suggest that shorter durations of adherence assessment (≤6 months) may be less accurate at predicting virological outcome. Moreover, PAMs are more likely to accurately predict outcomes at the end of a period of adherence assessment than at future time points. Not surprisingly, the balance of studies suggests that PAMs are superior to self-reported adherence in predicting virological outcome. Finally, a threshold effect for mortality is observed at adherence levels of 70%–80%, in contrast to virological outcomes, for which no adherence thresholds were observed.
PAM-based adherence estimates can be used by pharmacists and other health care providers to promote ART adherence. Although the literature on pharmacist-directed interventions is limited, pharmacy-based adherence interventions have successfully combined adherence education [53
], tailoring regimens to patient lifestyles [54
], and the management of adverse drug reactions [55
], resulting in improved adherence [53
] and improved virological [53
] and immunological [55
] response. Further investigation of these interventions is warranted in HICs and in LMICs where similar interventions have not been reported.