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.