In depth analysis of the effect of HIV infection on the frequency of mycobacteria-specific cells producing distinct cytokine combinations revealed a predominant reduction of IFN-γ single positive cells, for all antigens, in HIV-infected participants (median fold reduction of 3.2, 10 and 5.6 for ESAT-6/CFP-10, PPD and BCG, respectively) as well as a lower frequency of IFN-γ+IL-2+ cells (median fold reduction of 2.4, 5.9 and 2 for ESAT-6/CFP-10, PPD and BCG, respectively). Here, IFNG is linked to HIV infectious disease.