Strategies to Improve PrEP Adherence in People Who Use Drugs: A Systematic Review.

People who use drugs (PWUD) face a disproportionately high risk of HIV, accounting for a considerable share of cases in the United States. Pre-exposure prophylaxis (PrEP) has been shown to be effective in preventing HIV transmission through both sexual contact and injection drug use. However, adherence is essential for real-world success. Following PRISMA guidelines, we conducted the first systematic review to examine PrEP interventions among PWUD and identify strategies to enhance adherence. Using EMBASE, PubMed, and ClinicalTrials.gov databases, we screened 1,389 abstracts, of which nine met the inclusion criteria. The nine studies analyzed demonstrated extensive heterogeneity in intervention components, program duration, adherence measures, and outcomes. Most interventions aimed to reduce out-of-pocket costs and improve medication accessibility, while nearly half incorporated digital or electronic tools. Successful interventions addressed financial and logistical barriers and were implemented in regions where PrEP had been integrated into national healthcare systems at no additional cost. Additionally, combining PrEP with opioid substitution therapy or medication for opioid use disorder was associated with higher adherence rates, ranging from 80 to 95% of participants. Behavioral interventions were underutilized, despite their potential to address psychosocial challenges. Finally, unique barriers faced by women who use drugs highlight the need for tailored, trauma-informed, and mental health support services to address gender-specific challenges. Ultimately, these studies serve as an important starting point, underscoring both the necessity of broader research and the potential effectiveness of targeted programs to achieve and maintain high PrEP adherence for this key population.