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This study analyzes how the COVID-19 pandemic affected sexual behavior and use of HIV prevention methods among young transgender women (YTGW) and young gay, bisexual and other men who have sex with men (YGBMSM) participating in an HIV pre-exposure prophylaxis (PrEP) demonstration study in Brazil. Online interviews with 39 participants aged 15–22 years old were conducted between September and November 2020 and analyzed based on social constructionism and human rights-based approaches to health. The pandemic disrupted interviewees' routines, negatively affecting their life conditions. Among those who did not have a steady partner, social distance measures led to temporary interruption of sexual encounters and increased sexting and solo sex. Conversely, for those who had a steady relationship such measures contributed to increasing sexual practices and intimacy. Participants who had sexual encounters during the pandemic reported having continued to use PrEP. However, home confinement with family, lack of privacy, loss of daily routines and changes in housing impaired PrEP adherence and attendance at follow-up consultations. These results highlight the importance of maintaining HIV-service delivery for these groups during a public health crisis, as well as to address the structural drivers of the epidemic with comprehensive HIV prevention policies and by ensuring access of YGBMSM and YTGW to social protection policies. [ABSTRACT FROM AUTHOR]