CD4 and Granuloma: Mechanisms in addition to CD4+ T cell depletion that have been implicated in the synergistic interactions between Mtb and HIV include: disruption of the pro- and anti-inflammatory cytokine balance, impairment of CD4+ T cell and Mtb-specific T cell functionality, Mtb-induced increase in HIV viral load, viral evolution within granulomas, chronic immune activation, and HIV impairment of innate immune cells (23–26, 28, 30, 32, 35, 39, 40).