Inflammatory profile of HIV uninfected and co-infected patients with tuberculosis: a prospective cohort study and immunological network analysis

Background Human immunodeficiency virus type 1 (HIV-1) mediated dysregulation of the immune response to tuberculosis (TB) and its effect on the response to antitubercular treatment (ATT) is incompletely understood. Our aim was to perform an in-depth analysis of the inflammatory profile of HIV-1-uninfected and co-infected TB patients undergoing ATT, with sub-analysis of the effect of antiretroviral therapy and HIV-1 viraemia in the latter group. Methods An extensive panel of inflammatory markers were measured in plasma of a prospective patient cohort undergoing ATT at Khayelitsha Site B Clinic, South Africa between March 2013 and July 2014. Plasma samples were collected at baseline (1-5 days after commencing ATT), week 8 and week 20 of ATT. We applied network and multivariate analysis to investigate the dynamic inflammatory profile of these patients in relation to ATT and by HIV status. Findings HIV-1 status markedly influenced the inflammatory profile regardless of ATT duration. HIV-1 viral load emerged as a major factor driving differential inflammatory marker expression and impacting on correlation profiles observed in the HIV-1 co-infected group. Unexpectedly, IL-17A emerged as a key correlate of HIV-1 induced inflammation during HIV-TB co-infection. We validated these findings in a second cohort of hospitalized HIV-TB co-infected patients where the number of statistically significant correlations with IL-17A in network analysis predicted mortality. Interpretation Our findings demonstrate the effect of HIV-1 co-infection on the complexity of plasma inflammatory profiles in TB patients. Through network analysis we identified IL-17A as an important node in HIV-TB co-infection, thus implicating this cytokine’s capacity to correlate with, and regulate, other inflammatory markers. Further mechanistic studies are thus required to identify specific IL-17A related inflammatory pathways mediating immunopathology in HIV-TB co-infection, which may illuminate targets for future host directed therapies