Adherence measurement considerations for oral antiretroviral medications

[...]analysis of biological samples from the active arms indicated much lower PrEP use (unquantifiable or low drug concentrations), and particularly low use among participants who seroconverted. [...]this type of biomarker can be combined with short half-life drug concentrations to identify white-coat dosing. The PURPOSE-1 study, where some intentional non-adherence was possible, reported granular adherence data based on TFV-DP in DBS, as well as an adherence-efficacy relationship for F-TAF [1]. [...]does the requirement to cooperate with the adherence assessment influence the individual's willingness to participate in the study? Table 1 Main pros and cons of adherence measurements as they relate to non-adherence [6, 8, 10–14] Adherence measure Objective or subjective Pro Con Urine drug screening Objective Confirms ingestion; potential for rapid immunoassay at point of care Only detects if dose was ingested in previous 24–48 hours; white-coat dosing Plasma drug concentration Objective Confirms ingestion; sensitive assay can detect dose from 7 to 14 days in past Only detects most recent dose; white-coat dosing Dried blood spot testing Objective Agnostic to intentional versus unintentional non-adherence; confirms cumulative ingestions; well-studied Specific to tenofovir; some overlap in adjacent adherence categories; cannot discern non-adherence patterns Hair testing Objective Agnostic to intentional versus unintentional non-adherence; confirms cumulative ingestions; potential to test any drug; potential to assess drug along hair shaft for adherence patterns Less pharmacokinetics information to guide interpretation; some overlap in adjacent categories; need to donate hair Digital pills Objective Confirms ingestion; captures dosing patterns; high accuracy Requires participant cooperation; potential malfunction Electronic monitors Objective Captures dosing patterns Requires some participant cooperation; potential malfunction; does not confirm ingestion Directly observed/video observed Objective Captures dosing patterns Requires participant cooperation; intrusive; may not confirm ingestion (e.g. cheeking dose) Self-reporting Indirect Convenient; inexpensive Social desirability bias; recall limitations Pill count Indirect Convenient; inexpensive; unannounced counts more reliable Susceptible to manipulation particularly for announced counts; unannounced counts intrusive; does not confirm ingestion Medication possession ratio Indirect Convenient; inexpensive Does