Factors driving pre-exposure prophylaxis uptake among students at six Gauteng province universities: An application of Pender’s Health Promotion Model

<i>Background</i>: South Africa has the world's highest HIV prevalence rate (12.7%), with university students disproportionately affected. While HIV Pre-Exposure Prophylaxis (PrEP) is an effective preventive measure for high-risk individuals, its uptake among university students remains low, which hinders progress toward national and global targets to end the AIDS epidemic by 2030. This study aimed to identify the factors influencing PrEP uptake in this vulnerable population, specifically among university students in Gauteng province, using Pender's Health Promotion Model.<i>Methods</i>: A quantitative, descriptive cross-sectional survey was conducted among 537 university students across six universities in Gauteng province. Data were analysed using Partial Least Squares Structural Equation Modelling to identify significant predictors of PrEP use.<i>Results</i>: The study revealed a low PrEP uptake rate among students at risk of contracting HIV. The analysis identified several factors that directly influenced PrEP uptake, including knowledge (<i>β</i> = 0.122, <i>p</i> = 0.001), interpersonal influence (<i>β</i> = 0.082, <i>p</i> = 0.038), situational influence (<i>β</i> = 0.145, <i>p</i> = 0.001), and perceived benefits (<i>β</i> = 0.121, <i>p</i> = 0.003). Significant interactions were also found between condom use and knowledge (<i>β</i> = 0.098, <i>p</i> = 0.004) and between condom use and perceived benefits (<i>β</i> = 0.127, <i>p</i> = 0.013).<i>Conclusion</i>: PrEP uptake is a complex process influenced by the dynamic interplay of factors consistent with Pender's Health Promotion Model, particularly interpersonal, cognitive, and situational factors. These results provide valuable evidence for developing multifaceted, youth-friendly interventions, such as a mobile health application, to promote PrEP use, reduce HIV incidence, and help achieve national and global HIV prevention targets.