Fil: Eldholm, Vegard. Norwegian Institute of Public Health. Division of Infectious Disease Control; Noruega.Fil: Rieux, Adrien. University College London. UCL Genetics Institute; Reino Unido.Fil: Monteserin, Johana. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: López, Julia Montana. University College London. UCL Genetics Institute; Reino Unido.Fil: Palmero, Domingo. Hospital Muñiz. División Tisioneumonología; Argentina.Fil: Lopez, Beatriz. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: Ritacco, Viviana. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: Didelot, Xavier. Imperial College London. Department of Infectious Disease Epidemiology; Reino Unido.Fil: Balloux, Francois. University College London. UCL Genetics Institute; Reino Unido.The tuberculosis (TB) epidemic is fueled by a parallel Human Immunodeficiency Virus (HIV) epidemic, but it remains unclear to what extent the HIV epidemic has been a driver for drug resistance in Mycobacterium tuberculosis (Mtb). Here we assess the impact of HIV co-infection on the emergence of resistance and transmission of Mtb in the largest outbreak of multidrug-resistant TB in South America to date. By combining Bayesian evolutionary analyses and the reconstruction of transmission networks utilizing a new model optimized for TB, we find that HIV co-infection does not significantly affect the transmissibility or the mutation rate of Mtb within patients and was not associated with increased emergence of resistance within patients. Our results indicate that the HIV epidemic serves as an amplifier of TB outbreaks by providing a reservoir of susceptible hosts, but that HIV co-infection is not a direct driver for the emergence and transmission of resistant strains.