A pilot randomized controlled trial of PrEP Zingisa: Protocol for an adherence intervention that addresses transdiagnostic psychological barriers to consistent PrEP use during pregnancy and the postpartum transition among women in Cape Town, South Africa.

BackgroundSouth Africa has the largest HIV epidemic globally, and pregnant and postpartum individuals face high risk for new infections. Although daily pre-exposure prophylaxis (PrEP) is effective in preventing HIV, adherence during pregnancy and postpartum is often compromised. Depression and posttraumatic stress disorder (PTSD), common in this population, can interfere with PrEP use. Evidence-based approaches addressing psychological barriers are needed to improve PrEP adherence and persistence during this high-risk period.ObjectivesThis paper describes the protocol for a pilot trial to examine the feasibility and acceptability of PrEP Zingisa, a cognitive behavioral intervention targeting transdiagnostic mechanisms underlying depression/PTSD.DesignIn a randomized controlled trial, 70 pregnant individuals aged 15 and older who have recently initiated PrEP or experienced adherence challenges with moderate to severe depression and/or PTSD will be randomized to PrEP Zingisa or enhanced wait list control (WLC).MethodsPrEP Zingisa consists of four sessions focused on PrEP adherence skills and cognitive behavioral strategies to reduce withdrawal and avoidance. Sessions are delivered individually or in groups by a non-specialist provider. The WLC condition includes a PrEP education handout and mental healthcare referrals; WLC participants will be offered PrEP Zingisa LITE, a single-session version of the intervention. Primary outcomes include feasibility (interventionist fidelity, attendance, retention) and acceptability (participant/provider feedback), assessed two months post-baseline. Secondary outcomes include self-reported PrEP adherence, PrEP persistence, and depression/PTSD symptoms two months post-baseline and three months postpartum. Logistic and generalized linear mixed models will examine intervention effects and potential mediators.ResultsThis is a protocol paper, therefore results are not yet available.ConclusionThis trial will provide insight on feasibility, acceptability, and preliminary effectiveness of integrating a mental health-informed adherence intervention into routine antenatal and PrEP services. Findings will be disseminated through publications, presentations, and community partner engagement.