Barriers to Pre-Exposure Prophylaxis Uptake Among High-Risk Populations

Abstract

Pre-exposure prophylaxis (PrEP) has been shown, across successive oral and long-acting injectable formulations, to reduce HIV acquisition risk by well over 90% when used as directed, yet uptake among the populations it was developed for remains far below eligibility in the United States and globally. This article synthesizes the literature on why that gap persists, tracing PrEP's efficacy evidence from the foundational oral trials through the cabotegravir and lenacapavir injectable trials, then examining the individual, interpersonal, and structural barriers documented across Black men who have sex with men, transgender communities, people who inject drugs, cisgender women, and adolescents. We find that only around a quarter of PrEP-eligible people in the United States have been prescribed it, that stigma and medical mistrust operate as distinct but compounding barriers separate from cost and geographic access, and that these barrier categories combine differently across subpopulations rather than applying uniformly. Long-acting injectable formulations meaningfully address daily-adherence burden but leave most other documented barriers, including provider readiness, clinic-visit dependency, and population-specific access constraints, substantially unresolved. Closing the uptake gap, on this evidence, requires differentiated, population-specific intervention rather than a single structural or biomedical fix.