South Africa grapples with a substantial HIV burden, with young women disproportionately affected. Oral pre-exposure prophylaxis (PrEP) is an effective preventive measure; however, limited research has examined the obstacles and reservations around its usage.

This qualitative investigation delved into the impediments and apprehensions regarding oral PrEP among young women aged 18-24 in Amajuba district, KwaZulu-Natal, South Africa. In 12 in-depth interviews, the study used a social-ecological model to gauge oral PrEP awareness, assess attitudes, explore initiation determinants, pinpoint concerns, examine health system-related factors contributing to low uptake and solicit suggestions to enhance delivery.

The research identified barriers across various spheres. Individually, 67% of respondents lacked sufficient oral PrEP knowledge and had concerns about daily pill routines, forgetfulness and side effects. Institutional issues encompassed waiting times, privacy, confidentiality and staff attitudes. Misinformation and stigma also posed challenges, while most participants highlighted policy inadequacies.

The study underscored multifaceted barriers in the social-ecological framework, offering valuable insights for policymakers, stakeholders and programme managers in crafting youth-friendly interventions to bolster oral PrEP uptake.