TABLE 1.

How does HIV increase TB risk?

Hypothesis and exptl evidenceReference(s)
HIV replication is increased at sites of M. tuberculosis infection, leading to increased pathology
    Greater HIV p24 levels and viral loads in BAL fluid cells from TB-involved lungs than in BAL
        fluid from uninvolved lungs69
    Greater HIV loads in pleural fluid than in plasma from individuals with pleural TB52
    Greater HIV replication in stimulated macrophages infected with M. tuberculosis and HIV
        than in macrophages infected with HIV alone43, 44
HIV induces primary or reactivated TB through killing of CD4 T cells within granulomas
    HIV+ individuals with fewer peripheral CD4 T cells are more prone to TB than HIV+
        individuals with more CD4 T cells51
    Correlation between acute peripheral CD4 T cell count and reactivation of latent TB23
    Coinfected individuals have fewer BAL fluid CD4 T cells than individuals with TB alone46, 49
    Monkeys coinfected with SIVmac251 and M. tuberculosis have fewer CD4 T cells in granulomatous
        tissue than monkeys with active TB alone23
HIV manipulation of macrophage function prevents M. tuberculosis killing
    HIV/M. tuberculosis-coinfected macrophages induce less TNF-dependent apoptosis than
        macrophages infected with only M. tuberculosis48, 72, 73
    Coinfected macrophages release less TNF than macrophages infected with only M. tuberculosis48, 73
    HIV decreases the ability of M. tuberculosis-infected macrophages to acidify vesicles22, 67
HIV induces functional changes in M. tuberculosis-specific T cells that decrease their ability
        to contain M. tuberculosis
    Fewer IFN-γ+ M. tuberculosis-specific memory CD4 T cells after HIV infection in individuals
        with latent TB29, 30
    Fewer IFN-γ-TNF-IL-2 polyfunctional BCG-specific CD4 T cells in airways of HIV+ individuals
        than in those of HIV individuals46
    Lower IFN-γ mRNA production and cellular proliferation in airways of patients with AIDS and
        TB than in those of individuals with TB alone4, 17
    Lower IFN-γ, TNF, and IL-2 production and cellular proliferation in M. tuberculosis-specific peripheral T cells
        in HIV+ individuals than in HIV individuals with active TB30, 40, 65, 111