The evolution of Mycobacterium tuberculosis presents several challenges for public health. HIV and resistance to antimycobacterial medications have evolutionary implications for how Mycobacterium tuberculosis will evolve, as these factors influence the host environment and transmission dynamics of tuberculosis strains. We present an evolutionary invasion analysis of tuberculosis that characterizes the direction of tuberculosis evolution in the context of different natural and human-driven selective pressures, including changes in tuberculosis treatment and HIV prevalence. We find that the evolution of tuberculosis virulence can be affected by treatment success rates, the relative transmissibility of emerging strains, the rate of reactivation from latency among hosts, and the life expectancy of hosts. We find that the virulence of tuberculosis strains may also increase as a consequence of rising HIV prevalence, requiring faster case detection strategies in areas where the epidemics of HIV and tuberculosis collide.