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To outline the need for a new tuberculosis (TB) vaccine; challenges for induction of vaccine-mediated protection in HIV-infected persons; and recent advances in clinical development.HIV has a detrimental effect on T-cell function, polarization and differentiation of Mycobacterium tuberculosis (Mtb)-specific T cells, Mtb antigen presentation by dendritic cells, and leads to B-cell and antibody-response deficiencies. Previous observations of protection against TB disease in HIV-infected persons by Mycobacterium obuense suggest that an effective vaccine against HIV-related TB is feasible. Studies of inactivated mycobacterial, viral-vectored and protein subunit vaccines reported lower immune responses in HIV-infected relative to HIV-uninfected individuals, which were only partially restored with antiretroviral therapy. Bacille Calmette Guerin (BCG) revaccination of HIV-uninfected adolescents recently showed moderate efficacy against sustained Mtb infection, but live mycobacterial vaccines have an unfavorable risk profile for HIV-infected persons. Ongoing trials of inactivated mycobacterial and protein-subunit vaccines in HIV-uninfected, Mtb-infected adults may be more relevant for protection of HIV-infected populations in TB endemic countries.New TB vaccine candidates have potential to protect against HIV-related TB, through vaccination prior to or after HIV acquisition, but this potential may only be realized after efficacy is demonstrated in HIV-uninfected populations, with or without Mtb infection.