Latent and Active Tuberculosis Infection Increase Immune Activation in Individuals Co-Infected with HIV

Below:  A) representative flow cytometry plots of CD38 and HLA-DR expression on CD8 + (top panel) and CD4 + (bottom panel) T-cells from HIV-infected individuals with no evidence of M. tbinfection (no TB), latent TB (LTBI), or active TB (AT). Percentage of CD8 + (B) and CD4 + (D) T-cells expressing CD38 in no TB, LTBI, or AT individuals. Percentage of CD8 + (C) and CD4 + (E) T-cells co-expressing CD38 and HLA-DR in no TB, LTBI, or AT individuals. Subjects represented here were matched for CD4 + T-cell count and HIV viral load, and were members of the iThimba or TB String Study cohorts. p-Values reported for Mann Whitney U test, with p-values greater than 0.05 not displayed. Data displayed as median with interquartile range.

In recent years, chronic immune activation and systemic inflammation have emerged as hallmarks of HIV disease progression and mortality. Several studies indicate that soluble inflammatory biomarkers (sCD14, IL-6, IL-8, CRP and hyaluronic acid), as well as surface markers of T-cell activation (CD38, HLA-DR) independently predict progression to AIDS and mortality in HIV-infected individuals. While co-infections have been shown to contribute to immune activation, the impact of latent tuberculosis infection (LTBI), which is widely endemic in the areas most affected by the global AIDS epidemic, has not been evaluated. We hypothesized that both active and latent states of Mycobacterium tuberculosis co-infection contribute to elevated immune activation as measured by these markers. In HIV-infected individuals with active, but not latent TB, we found elevated levels of soluble markers associated with monocyte activation. Interestingly, T-cell activation was elevated individuals with both latent and active TB. These results suggest that in the highly TB- and HIV-endemic settings of southern Africa, latent TB-associated T-cell activation may contribute to HIV disease progression and exacerbate the HIV epidemic. In addition, our findings indicate that aggressive campaigns to treat LTBI in HIV-infected individuals in high-burden countries will not only impact TB rates, but may also slow HIV progression.

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