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BackgroundHIV incidence rates have increased in adolescent men who have sex with men (AMSM) and adolescent transgender women (ATGW). Thus, it is essential to promote access to HIV prevention, including pre-exposure prophylaxis (PrEP), among these groups. Moreover, using artificial intelligence and online social platforms to create demand and access to health care services are essential tools for adolescents and youth. ObjectiveThis study aims to describe the participative process of developing a chatbot using artificial intelligence to create demand for PrEP use among AMSM and ATGW in Brazil. Furthermore, it analyzes the chatbot’s acceptability, functionality, and usability and its results on the demand creation for PrEP. MethodsThe chatbot Amanda Selfie integrates the demand creation strategies based on social networks (DCSSNs) of the PrEP1519 study. She was conceived as a Black transgender woman and to function as a virtual peer educator. The development process occurred in 3 phases (conception, trial, and final version) and lasted 21 months. A mixed methodology was used for the evaluations. Qualitative approaches, such as in-depth adolescent interviews, were used to analyze acceptability and usability, while quantitative methods were used to analyze the functionality and result of the demand creation for PrEP based on interactions with Amanda and information from health care services about using PrEP. To evaluate Amanda’s result on the demand creation for PrEP, we analyzed sociodemographic profiles of adolescents who interacted at least once with her and developed a cascade model containing the number of people at various stages between the first interaction and initiation of PrEP (PrEP uptake). These indicators were compared with other DCSs developed in the PrEP1519 study using chi-square tests and residual analysis (P=.05). ResultsAmanda Selfie was well accepted as a peer educator, clearly and objectively communicating on topics such as gender identity, sexual experiences, HIV, and PrEP. The chatbot proved appropriate for answering questions in an agile and confidential manner, using the language used by AMSM and ATGW and with a greater sense of security and less judgment. The interactions with Amanda Selfie combined with a health professional were well evaluated and improved the appointment scheduling. The chatbot interacted with most people (757/1239, 61.1%) reached by the DCSSNs. However, when compared with the other DCSSNs, Amanda was not efficient in identifying AMSM/ATGW (359/482, 74.5% vs 130/757, 17.2% of total interactions, respectively) and in PrEP uptake (90/359, 25.1% vs 19/130, 14.6%). The following profiles were associated (P |