HIV Pre-exposure Prophylaxis (PrEP) uptake among transgender (TG) people and gay men and other men who have sex with men (MSM) remains low, despite South Africa being the first African country to approve PrEP. This mixed-methods study used a two-phase explanatory sequential design: (1) quantitative analysis of cross-sectional surveys followed by (2) qualitative in-depth interviews. This study explored facilitators and barriers to PrEP uptake to identify strategies to increase utilization in these key populations. We conducted 202 cross-sectional surveys and 20 in-depth interviews between July 2021 and March 2022 in Soshanguve, Tshwane, Gauteng. Quantitative data were analyzed using univariate logistic regression; thematic analysis was performed for qualitative data. Findings show high willingness to use PrEP but low PrEP uptake. We outline strategies to facilitate PrEP use: (1) demystify daily PrEP by deploying community-engaged PrEP education campaigns; (2) capitalize on existing peer networks; and (3) expand accessible and culturally responsive PrEP service delivery models. We provide feasible recommendations to close the PrEP uptake gap in these key populations in South Africa.

尽管南非是第一个批准 PrEP 的非洲国家，但跨性别者 (TG) 和男同性恋者及其他男男性行为者 (MSM) 对 HIV 暴露前预防 (PrEP) 的采用率仍然较低。这项混合方法研究采用了两阶段解释性序贯设计：（1）横断面调查的定量分析，然后是（2）定性深入访谈。本研究探讨了 PrEP 吸收的促进因素和障碍，以确定提高这些关键人群利用率的策略。2021 年 7 月至 2022 年 3 月期间，我们在豪登省茨瓦内市的 Soshanguve 进行了 202 项横断面调查和 20 次深度访谈。使用单变量逻辑回归分析定量数据；对定性数据进行了主题分析。研究结果显示使用 PrEP 的意愿较高，但 PrEP 的使用率较低。我们概述了促进 PrEP 使用的策略：(1) 通过部署社区参与的 PrEP 教育活动来揭开日常 PrEP 的神秘面纱；(2) 利用现有的同行网络；(3) 扩大可获取且具有文化适应性的 PrEP 服务提供模式。我们提供可行的建议，以缩小南非这些重点人群的 PrEP 吸收差距。