Background. HIV-1 infected persons are more susceptible to tuberculosis (TB) than HIV-1-uninfected persons. Low peripheral (p)CD4 T cell count is not the sole cause of higher susceptibility because HIV-1 infected persons with high pCD4 and those prescribed successful anti-retroviral therapy (ART) remain more prone to active TB than HIV-1-uninfected persons. We hypothesized that the increase in susceptibility is caused by HIV-1's ability to manipulate the M. tuberculosis (Mtb) granuloma.

Methods. We examined 71 excised cervical lymph nodes (LN) from HIV-1-TB-co-infected and singly-HIV-1 or TB-infected persons with a spectrum of pCD4 counts and ART status. We quantified differences in Mtb, HIVp24, cellular and cytokine presence.

Results. HIV-1 increased Mtb bacillary numbers and reduced CD4 T cell counts within granulomas. pCD4 depletion correlated with granulomas that contained fewer CD4 and CD8 T cells, less IFN-gamma, more neutrophils, more IL-10 and increased Mtb bacilli. Mtb numbers correlated positively with IL-10 and IFN-alpha, and fewer CD4 and CD8 T cells. ART reduced IL-10 production.

Conclusion. pCD4 depletion correlated with increased Mtb bacilli presence, IL-10 production, and other phenotypic changes within granulomas, demonstrating HIV-1 infection progressively changes these granulomas.