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Tijuana, Mexico, has a concentrated HIV epidemic among overlapping key populations (KPs) including people who inject drugs (PWID), female sex workers (FSW), their male clients, and men who have sex with men (MSM). We developed a dynamic HIV transmission model among these KPs to determine the extent to which their unmet prevention and treatment needs is driving HIV transmission. Over 2020–2029 we estimated the proportion of new infections acquired in each KP, and the proportion due to their unprotected risk behaviours. We estimate that 43.7% and 55.3% of new infections are among MSM and PWID, respectively, with FSW and their clients making-up < 10% of new infections. Projections suggest 93.8% of new infections over 2020–2029 will be due to unprotected sex between MSM or unsafe injecting drug use. Prioritizing interventions addressing sexual and injecting risks among MSM and PWID are critical to controlling HIV in Tijuana.   Supplementary Information  The online version contains supplementary material available at 10.1007/s10461-021-03361-2.

Overlapping Key Populations and HIV Transmission in Tijuana, Mexico: A Modelling Analysis of Epidemic Drivers