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The Region of the Americas has been a pioneer in its response to HIV and has achieved admirable results. However, serious challenges persist that require urgent attention if we are to end AIDS by 2030. The encouraging trend of declining new HIV infections since the early 2000s has plateaued over the past five years, and indeed in-depth analysis shows a small increase in new HIV infections among adult males in both Latin America and the Caribbean. There is currently a broad range of biomedical tools available to prevent and treat HIV, but to end the AIDS epidemic, structural barriers and social determinants of health also need to be convincingly addressed.