Reframing HIV prevention: a narrative synthesis review using the 5C vaccine hesitancy framework to understand and measure HIV pre-exposure prophylaxis hesitancy

Background: HIV pre-exposure prophylaxis (PrEP) is an effective biomedical prevention strategy, but uptake remains low among key populations, raising concerns about PrEP hesitancy. This review examines the relevance of the 5C Vaccine Hesitancy Framework in explaining psychosocial and contextual factors influencing PrEP hesitancy. Objective: To apply the 5C Vaccine Hesitancy Framework to better understand reasons for PrEP hesitancy. Method: A systematic search was conducted in May 2025 across PubMed, Google Scholar, Scopus, and Sage Journal. English-language studies published between 2010 and May 2025 were included using the keywords ‘HIV', ‘PrEP', ‘acceptance', ‘rejection', ‘refusal', and ‘uptake’. Findings from 162 studies were synthesized narratively. Results: Confidence was influenced by mistrust in healthcare providers and concerns about side effects. Complacency arose from low perceived HIV risk. Constraints included cost, stigma, and restrictive policies. Calculation reflected trade-offs between protection, pill burden, and stigma. Collective responsibility was supported by peers and communities but undermined by family stigma. Additional barriers included privacy concerns, digital literacy, and service delivery preferences, while mHealth and differentiated care models showed promise. Conclusions: The 5C Framework is a useful model for understanding PrEP hesitancy and informing context-specific interventions and tailored measurement tools to improve Pr EP uptake.

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