Serum tuberculosis biomarkers and their association with clinical characteristics among hospitalized adults living with HIV in Uganda

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Background Diagnosis of pulmonary tuberculosis (PTB) among people living with HIV (PLHIV) remains challenging, particularly in high TB/HIV burden settings. We evaluated serum biomarkers associated with active PTB and their relationship with TB-related clinical characteristics among hospitalized PLHIV in Uganda. Methods We analysed archived serum samples from adult PLHIV ( n = 60) categorized into three groups (20 each): (i) sputum culture and/or GeneXpert-confirmed PTB (active PTB), (ii) presumptive TB with negative TB culture/GeneXpert (symptomatic PTB-negative), and (iii) asymptomatic PLHIV attending routine HIV care (asymptomatic PLHIV controls). Inflammatory biomarkers including C-reactive protein (CRP) and leptin as well as immune activation markers (interferon gamma–induced protein 10 -IP-10 and β2-microglobulin) were quantified using enzyme-linked immunosorbent assay and Bio-Plex Pro assays. Biomarker levels were compared between active PTB and TB-negative groups. Logistic regression identified biomarkers independent associations with active PTB and Spearman rank correlation assessed biomarkers correlations with TB-related clinical characteristics among active PTB participants. Results Median serum concentrations of IP-10 (19,566 pg/mL; p = 0.001), β2-microglobulin (33.9 ng/mL; p = 0.023), and CRP (1.77 mg/dL; p = 0.05) were significantly higher among active PTB participants compared to symptomatic PTB-negatives and asymptomatic PLHIV controls. Conversely, leptin levels were significantly lower in the active PTB (35.0 pg/mL) than in asymptomatic PLHIV controls (102.4 pg /mL; p = 0.001). IP-10 (adjusted odds ratio-aOR 2.74; 95% CI: 1.54–4.88; p < 0.001) and β2-microglobulin (aOR 2.09; 95% CI: 1.13–3.86; p = 0.019) were the strongest independent predictors of active PTB. Biomarker concentrations did not correlate significantly with TB-related clinical characteristics. Conclusion IP-10, β2-microglobulin, and CRP were elevated in PLHIV with active PTB, whereas leptin levels were reduced. These biomarkers did not correlate with clinical characteristics. Our findings show that serum biomarkers may aid in identifying PTB among hospitalized PLHIV but with limited value in assessing clinical presentation. Further research is warranted to rigorously evaluate their diagnostic performance in both simple and combined biomarkers models and to evaluate their point-of-care utility for TB screening and timely treatment initiation in hospitalized PLHIV.

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