“I’ll Continue If I Have a Positive Mind”: Identifying the Ways in Which Depression and PTSD Impact PrEP Adherence Among PrEP-Experienced Pregnant and Postpartum Women in Cape Town, South Africa

Pregnant and postpartum people (PPPs) face heightened risk for HIV acquisition, yet depression and trauma-related symptoms can undermine adherence to pre-exposure prophylaxis (PrEP). To inform the development of a brief mental health-focused adherence intervention, we explored the impacts of depression and posttraumatic stress disorder (PTSD) symptoms on PrEP use among PPPs in Cape Town, South Africa. Twenty-eight PPPs with elevated symptoms of depression and/or PTSD and recent PrEP adherence challenges completed qualitative interviews. Six antenatal providers were also interviewed. Thematic analysis revealed three key findings with subthemes that deepen exploration of each theme: (1) depression and PTSD symptoms contributed to missed PrEP doses or late pickups by increasing doubt about PrEP efficacy, amplifying pill burden, intensifying avoidance and withdrawal (e.g., hypersomnia and disengagement from providers), and disrupting memory through rumination and emotional overload; (2) most PPPs preferred support from professional counselors, while a minority preferred informal support; and (3) intervention design considerations included aligning patient and provider goals, selecting between individual or group formats, and addressing integration barriers such as staffing and space constraints. Providers affirmed the need for embedded mental health support. Intervention strategies that increase PrEP knowledge and motivation while targeting emotional withdrawal, fatigue, and cognitive overload may improve adherence and reduce HIV risk in this population.