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Background: The border area between French Guiana and Brazil is an active HIV-transmission zone. The aim of the present study was to describe HIV knowledge, risk and the level of stigma among inhabitants of this border area.Methods: A cross-sectional study was conducted among 621 inhabitants over 18 years of age in the border cities of Saint-Georges-de-l'Oyapock in French Guiana and Oiapoque in Brazil. It was conducted between October 2017 and February 2018. An anonymous standardized questionnaire was filled out by culturally-trained mediators, then analyzed using STATA 12.Results: Almost half (45.9%) of the individuals had a low education level. Participants whose native language was Portuguese or French demonstrated better HIV knowledge than other populations, notably native Amerindian and creole-speaking people. HIV risk behavior was more frequent in men and in younger age groups. People with good HIV knowledge reported having performed more HIV tests in the last year than participants with poor knowledge. The stigma level was high and reported in 74.8% of respondents.Conclusions: These results illustrate the need for initiatives to improve HIV prevention among autochthonous populations on both sides of this border area. Cross-border collaboration on health policies could produce common key messages adapted to the education level and multi-linguistic populations who live in this area. [ABSTRACT FROM AUTHOR]