PA-543 Evaluation of host serum biomarkers from successfully treated TB patients presenting with or without persisting lung inflammation – preliminary findings of StatinTB trial

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Background Despite the availability of anti-TB treatment, successfully treated TB patients remain with persisting lung inflammation regardless of HIV status. Lung inflammation has been linked with robust or imbalanced host immune responses which exacerbate tissue necrosis. Soluble host biomarkers have been shown to correlate with the development of lung inflammation at different stages of anti-TB treatment which further affect sputum conversion in these patients. In our ongoing StatinTB trial (RIA2017T-2004; NCT04147286), we evaluate safety and efficacy of 40 mg atorvastatin to reduce persistent lung inflammation after TB treatment in HIV-/HIV+ adults measured by 18F-FDG-PET/CT. Here we aim to explore the expression profile of host serum biomarkers from successfully treated TB patients with or without persisting lung inflammation. Methods Study participants were screened for sputum conversion at month-4 and month-6 of anti-TB treatment. Enrolled participants were subjected to PET/CT scan, where Arm A=TLG<50SUVbw*ml (minimal lung inflammation) and Arm B=TLG≥50SUVbw*ml (persisting lung inflammation). A total of 71 participants (Arm A=42, Arm B=29) were evaluated in this study. Serum samples were collected after 1-week washout period following completion of anti-TB treatment. A panel of 48 biomarkers were evaluated using Luminex multiplex platform (Bioplex200). Results Twenty soluble biomarkers were differentially expressed between Arm A (TLG<50SUVbw*ml) and B (TLG≥50SUVbw*ml). These included 9 pro-inflammatory biomarkers,1 anti-inflammatory cytokine, 5 growth factors, 2 pleiotropic mediators and 3 chemokines. Using ROC curve, 14 biomarkers were identified as potential individual candidates to distinguish between Arm A and Arm B with AUC ranging between 0.702–0.833 where sensitivity ranged between 58.6–69.0% and specificity ranged between 71.4–81.0% at specific cut-off values. Conclusion This study highlights that successfully treated TB patients remain with persisting lung inflammation. These patients further present with different soluble biomarker profiles which may be driven by lung inflammation.

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