Performance of Adherence Measures for Oral, Tenofovir-Based HIV Pre-Exposure Prophylaxis: A Systematic Review

Accurate adherence measures to HIV pre-exposure prophylaxis (PrEP) are essential for identifying individuals with low adherence and providing tailored support. This systematic review summarizes evidence on the performance of PrEP indirect adherence measures and explores their potential use in clinical practice. Following a registered protocol (PROSPERO: CRD42020144733) we searched PubMed, Embase, LILACS and Web of Science until December 2024. We included studies that assessed PrEP adherence among individuals using daily oral PrEP with tenofovir disoproxil fumarate plus emtricitabine (TDF/FTC). The reference standard involved quantifying PrEP in dried blood spots or plasma, and index tests included self-reported adherence, pill counts, pharmacy records, electronic monitoring, or composite measures. We used QUADAS-2 to assess the risk of bias and applicability concerns. Twenty-three studies, which included 6649 individuals, fulfilled the inclusion criteria. Most were observational studies (n = 17, 73.9%), and the most common measure was self-report (n = 18, 78.3%). The performance of indirect measures was reported through accuracy statistics in 12 studies (52.2%), concordance in two (8.7%), correlation in eight (34.8%), and proportions in one (4.3%). The risk of bias and applicability concerns were generally low or unclear due to unclear reporting. This review underscores the wide heterogeneity of indirect measures used to assess PrEP adherence, with self-reports being the most frequently utilized. Despite some correlation with direct measures, these methods showed mixed evidence of accuracy, with studies reporting moderate discriminatory capacity for identifying high protective levels of TFV-DP. This finding limits the broader applicability of the measures and underscores the need for further research.