Table 1:

Comparison of Adherence Metrics

Measure	Advantages	Limitations	Implementation Concerns
HIV viral load	Assesses both HIV treatment efficacy and adherence Standard of care Point-of-care (POC) tests in development	May not reflect perfect adherence (which is optimal for durability, inflammation) Lag in viral load rise after non-adherence Not applicable to PrEP	Expensive and not universally available Usually centrally run, delays in results Not applicable to PrEP
Self-report	Used in routine care Cost-effective	Recall bias Social desirability bias Mostly overestimates adherence Cannot measure ingestion Inaccurate in PrEP/ HIV ART trials	Highly acceptable and simple to implement Computer assisted selfinterview may improve accuracy but additional cost/time
Pill Counts	Minimal training Quantitative	Easily manipulated Inaccurate in PrEP/HIV ART trials Cannot measure ingestion	Require staff time to perform
Pharmacy Refills	Can be performed retrospectively	Stockpiling can lead to overestimation of adherence Cannot measure ingestion	Requires central healthcare systems Pharmacy data must be integrated with clinical/research systems to be useful
Electronic Adherence Monitors	Reveal adherence patterns Some systems are realtime	Dependent on patient using device Large, bulky, not surreptitious Cannot measure ingestion Requires internet, electricity, charging	Requires special device Can be costly Transmission system maintenance
Ingestible electronic pills	Records time of ingestion Reveals adherence patterns Records physiologic parameters	Requires a relay device that may require patient adherence (i.e. using a patch)	Requires specialty pharmacy or industry for assembly Maintenance of bluetooth signal, smartphone
Pharmacologic measures (recent adherence: plasma, FTC-TP in DBS, urine)	Objectively assess recent adherence and pharmacokinetics Urine testing available at POC	Vulnerable to whitecoat dosing POC urine test is qualitative	Lab-based testing requires training and expensive machines POC test requires urine collection, so privacy
Pharmacologic measures (cumulative adherence: TFV-DP in PBMCs and DBS, antiretrovirals (ARVs) in hair)	Similar to above but assess cumulative dosing, i.e average adherence Hair can assess cumulative adherence to variety of ARVs Hair easy to collect in resource-limited settings	Need to combine with other metrics such as FTC-TP in DBS to assess patterns or perform segmental hair analysis Hematocrit, biologic sex may impact DBS levels Must have hair of sufficient length	DBS requires specialized training for collection and processing Expensive machines to run assays PBMCs difficult to collect/process/store