Investigating the dynamic inflammatory profile of tuberculosis patients with and without HIV-1 co-infection

In 2019 an estimated 360 000 South Africans developed tuberculosis (TB), 58% of whom were also living with HIV. That same year, 36 000 HIV-positive South Africans died of TB. Although antiretroviral therapy (ART) for HIV reduces the risk, people living with HIV remain at higher risk of developing TB than those who are HIV-negative.

The influence of HIV infection on the immune response to the bacterium that causes TB remains poorly understood, as each pathogen compounds the immunopathology associated with the other. It is therefore difficult to predict treatment outcomes in people living with HIV-TB co-infection. However, CIDRI-Africa researchers and colleagues used network analysis to investigate the effect of antitubercular therapy (ATT) on this inflammatory profile and the extent to which the HIV-induced immune response and ART alters the inflammatory profile in TB.

The team recruited two cohorts of TB patients from Khayelitsha, near Cape Town. The patients donated blood samples at the start of their ATT, and after 8 and 20 weeks. Plasma was isolated from the samples and then tested for the presence of 38 cytokines, acute phase proteins, and soluble receptors. Network analysis was applied to investigate the expression of these biomarkers at different timepoints and to assess the effects of TB and HIV co-infection, ART, and HIV viraemia on biomarker expression.

Results of the network analyses indicated that HIV viraemia is a key driver of inflammation during HIV-TB co-infection, regardless of duration of ATT. Suppression of HIV replication with ART diminished inflammatory network connectivity.

The cytokine interleukin-17A emerged as the most important node in the network analysis of the cohort overall, as well as in the ART naive and HIV virally unsuppressed subgroups. Increased IL-17A network connectivity was found to be indicative of elevated systemic inflammation and immune activation induced by advanced HIV infection, and predicted mortality in patients with HIV-tuberculosis co-infection.

This is the first time that IL-17A-related inflammatory networks have been shown to have an integral role in HIV-TB co-infection. However, much work remains to be done to elucidate the exact mechanism whereby IL-17A network connectivity is enhanced during co-infection and how HIV viraemia drives this effect.

 

Read the full paper here.

Du Bruyn E, Fukutani KF, Rockwood N, et al. Inflammatory profile of patients with tuberculosis with or without HIV-1 co-infection: a prospective cohort study and immunological network analysis. The Lancet Microbe 2021: doi.org/10.1016/S2666-5247(21)00037-9.