CD4+ T cell markers associated with Treatment Outcomes in Tuberculosis: A Sub-analysis of a Phase IIB Trial of Acetylsalicylic acid and Ibuprofen as Adjunctive Therapy.

BACKGROUND

Adjunctive host-directed therapies (HDT) may improve treatment outcomes in tuberculosis (TB). Affordable repurposed drugs can be quickly implemented in clinical practice; however, predictive biomarkers are essential for determining their potential effectiveness.

METHODS

72 patients (35.2% people with HIV) from South Africa with drug-sensitive pulmonary TB, recruited to the SMA-TB clinical trial of adjunctive acetylsalicylic acid (ASA) and ibuprofen (IBU), were included. CD4+ T cell subsets and Mtb-specific CD4+ T cell responses were analysed by flow cytometry at baseline, week 2, week 8 and week 24 and tested as predictors for microbiological, clinical and radiological outcomes.

RESULTS

Most TB patients experienced a fast sputum culture conversion and good clinical and radiological outcomes by week 24, regardless of intervention or HIV co-infection. During TB therapy, fractions of Mtb-specific polyfunctional CD4+ T cells, Th1 and Th1/Th17 subsets, and CD153 expression increased, whereas Ki67+HLA-DR+ CD4+ T cells declined. No statistically significant differences were identified between the ASA or IBU groups and placebo for any defined outcome. Still, higher baseline fractions of polyfunctional and CD153-expressing CD4+ T cells were associated with fast sputum culture conversion in the ASA and placebo arms.

CONCLUSIONS

CD4+ T cell subsets show promise as markers of disease severity and potential predictors of microbiological, clinical, and radiological outcomes in treated TB. However, the present findings are insufficient to support the routine use of ASA or IBU in adjunctive HDT regimens, and larger, targeted studies are warranted.