When and how should we be measuring adherence to antiretroviral therapy in resource-limited settings ?

The primary goal of treatment with antiretroviral therapy (ART) is to prevent HIV-related morbidity and mortality. The effectiveness of ART has been clearly demonstrated, as have the positive relationships between adherence to ART and viral suppression, increased CD4 cell count, positive clinical outcomes, and reduced mortality. More recently it has been shown to associated with reduced risk of transmission to uninfected partners. High levels of adherence are critical for successful treatment. Accordingly, for ART programs to achieve their population level goals, individual adherence must be monitored accurately and frequently and prompt action must be taken when poor adherence is identified.

needs. 14 Several approaches to monitoring adherence, including self-report, pill counts and lab monitoring are currently in use and meet each of these criteria to varying degrees, but none meets them all.
Self-report is the most commonly used method for measuring adherence in routine clinic settings. It has been shown to be reasonably well associated with viral suppression. 15, 16 Self-report data is easy to collect, inexpensive and flexible (questionnaires suit different language abilities) and can distinguish between nonadherence that is intentional (where the patient chooses not to take medicine, for example when they start to feel better or if it makes them feel worse) and unintentional (when the patient forgets about taking their medicine) 17 . This last point is important as nonadherence can be the result of several different underlying causes, each of which requires different interventions. 7,14 Despite its usefulness, self-report data tends to over-estimate adherence, [18][19][20] and typically only reflects short-term adherence. Future efforts around self -report must improve the sensitivity and specificity of the approach and address whether questionnaires to assess adherence remain valid when translated and modified for different populations (i.e. different ages, sexes, socioeconomic and educational backgrounds) and countries.
The visual-analogue scale, Likert item (rating scale), pills identification test (PIT) and medication possession ratio, briefly described below in Table 1, provide estimates of ART adherence which correlate reasonably well with HIV viral suppression. 21 These simple adherence measures are inexpensive and easy to administer. However, they require validation and adjustment prior to implementation in the routine clinical setting. On their own, surrogate noncomputerized methods such as pill-counts or Simplified Medication Adherence Questionnaires (SMAQ) all have strengths, but they also have drawbacks and limitations (Table 1). The same is true of computerized methods such as computer-assisted self-administered interviews 22 , electronic pill monitoring (micro-electronic monitoring), appointment keeping/missed visits, medication possession ratio, prescription refill days or dispensing records. Advanced technology, high cost and logistical requirements have precluded the wider application of some of these methods in sub-Saharan Africa. 23 An effective adherence program for resourcelimited settings may, therefore, require the combination or "triangulation" of a number of inexpensive surrogate and non-surrogate markers. 14 These, inexpensive and easy to administer markers may be incorporated into electronic patient management systems to flag patients at risk for virological failure due to poor adherence.
However, rigorous evaluation of these methods under routine clinical settings has yet to be conducted.
Laboratory markers provide another approach to assessing treatment adherence. Viral load is perhaps the best and most reliable indicator of poor adherence (through detection of circulating virus and treatment failure) but is expensive and not easily accessible or available in many resource-limited settings. 24  The PIT asks patients to examine a board displaying several pills for each antiretroviral drug and to identify which they have been taking.
Correct scores on the PIT have been shown to be associated with treatment adherence May overestimate the impact of overestimate the impact of socioeconomic factors (i.e. poor literacy on adherence)

Likert item (rating scale)
Participants are asked to report how closely they followed their specific schedule over the last 4 days using a 5-point scale, ranging from 1 (never) to 5 (all the time) Simple to administer. Less time-consuming than pillcounts Subject to the same errors and dishonesty found with selfreporting

Prescriptionrefill days or dispensing records
Provide the dates on which antiretroviral medications are dispensed. If refills are not obtained on time, it is assumed that the patient is not taking their medication between refills or is missing doses Analyzing dispensing records for drug distribution allows for a formal, less intrusive way of flagging nonadherence Does not tell you if patient took the medication, at the correct time with the appropriate dietary requirements Adherence continues to be a concern as the scale up of ART continues. At a programmatic level, adherence levels vary greatly across different social and cultural settings and from program to program with nonadherence rates ranging from 50-80%. 11, [45][46][47][48] Nonadherence has the potential to undermine the dramatic improvements in survival seen in resource-limited settings as ART becomes more widely available. 49 Understanding biomedical, social and cultural determinants of adherence in high-risk populations is urgently needed. 20