Abstract: Pre-exposure prophylaxis (PrEP) is a cornerstone of HIV prevention and includes a daily oral pill, intermittent dosing, a vaginal ring, and long-acting injectables. This narrative review is based on recent literature through November 1, 2025 and the World Health Organization (WHO) PrEP guidance from 2012 to 2025. We review how WHO has shaped global PrEP policy and service delivery, and implementation priorities in low- and middle-income countries (LMICs) with a focus on long-acting injectables. We summarize the shift toward differentiated service delivery and the evolution of HIV self-testing to support PrEP initiation, retention, and adherence. Persistent gaps in PrEP care include access to healthcare, stigma, limited awareness, costs, transportation, and medication burden. The long-acting era of PrEP is exciting and offers significant opportunity for HIV prevention. Current long-acting injectable PrEP formulations are still limited in most LMICs but recent progress on access and implementation is encouraging. Other long-acting formulations are in development. Priorities for PrEP implementation should include securing funding for and improving access to PrEP medications including long-acting formulations; cross-sector partnerships among governments, community-based organizations, pharmacies, and medical providers; and pro-access licensing, regional manufacturing and transparent pricing to ensure affordability in LMICs. Implementing these priorities will facilitate population-level HIV prevention and accelerate progress toward reducing HIV incidence.

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