Scaling up pre-exposure prophylaxis: A global analysis of processes and challenges regarding the implementation of the pre-exposure prophylaxis guidelines

Background: Pre-exposure prophylaxis (PrEP) guideline implementation varies widely across countries as a result of differences in health systems, resources, and HIV priorities. Since 2016, oral PrEP has been available to key populations, yet limited evidence exists on how implementation challenges differ across contexts. Objectives: This review aimed to explore the processes and challenges in the implementation of PrEP guidelines globally. Method: An integrative review method was used by searching electronic databases, including PubMed, Medline, EBSCOhost, CINAHL, and Google Scholar, to extract the data. We included qualitative, quantitative, and mixed-method studies relevant to the global implementation of PrEP published in peer-reviewed English journals from 2019 through 2025. Results: This study emphasises that worldwide PrEP implementation is complex and adaptable, involving progressive provider engagement, task-shifting, and health system integration. Stigma and misunderstandings about PrEP, including structural barriers such as a lack of coverage recognition and supply chain difficulties at odds with the maintenance phase needed to scale up availability, are challenges. Conclusion: Progress on global PrEP coverage has been blunted by persisting challenges in dismantling structural, financial, and geopolitical blockades to universal access. The model will work if it is implemented with community outreach and creative service delivery, including education, training, and outreach. Structural inequalities need to be considered and crisis-affected communities prioritised to ensure that access is equitable and sustainable. Implemented at scale, PrEP could be a game changer for HIV prevention globally, especially in high-burden countries. Contribution: This study contributes by synthesising evidence on global PrEP guideline implementation, highlighting health system, structural, and societal challenges.