Defining HIV Pre-Exposure Prophylaxis (PrEP) Persistence: A Scoping Review

When assessing the effectiveness of pre-exposure prophylaxis (PrEP) programmes, interventions, or modalities, it is important to understand patterns of PrEP use. Continued use of PrEP is frequently referred to as PrEP "persistence." But persistence is not defined consistently, and differences impact the interpretation of study outcomes and public health policy. We conducted a scoping review to describe and compare definitions of PrEP persistence.

We searched PubMed, Embase, Scopus and Global Health records (01/01/2012-01/26/2026) for results that discussed longitudinal anti-HIV agents for HIV prevention. We included HIV, prevention and text variations of "persist-." We screened abstracts for relevance, reviewed relevant full-text articles, and then extracted key outcomes. Screening and extraction were performed independently by two investigators; conflicts were reviewed and resolved by a third.

Our search returned 1549 de-duplicated results. We reviewed 362 full-text articles, yielding 147 studies for extraction. Approximately one-third (42/147, 29%) provided only qualitative persistence definitions. Among studies with operational definitions (105/147; 71%), three-quarters (80/105; 76%) considered a prescription refill and/or clinic visit date, and more than half (60/105; 57%) relied exclusively on these dates. Adherence (e.g. reported or measured drug taking) was commonly considered; 28% (29/105) of studies with an operational persistence definition included adherence assessment, and 11% (12/105) used only adherence to assess persistence. Thresholds used to classify persistent versus non-persistent PrEP use varied considerably.

Definitions of PrEP persistence are heterogeneous. Most considered engagement in PrEP services (e.g. a clinic visit or medication refill), but nearly one-third included or relied exclusively on adherence measures. The differences in definitions have important implications for cross-study comparisons.

The heterogeneity observed among persistence definitions complicates comparisons of PrEP interventions and related public health decision-making. A single consensus definition of persistence is unlikely to suit all study settings, objectives, and designs; however, interpretability and comparability of results could be improved by increasing transparency and consistency in reporting. Our findings emphasize the importance of capturing clinically relevant, prevention-effective use when possible and of rigorously considering the implications of a chosen persistence definition on estimates and associated conclusions.