Acute-Phase Proteins as Biomarkers of Inflammation in HIV Patients with Latent Tuberculosis: A Prospective Study

Nathella Pavan Kumar^1*Rajamariyam M¹Arul Nancy²Bubby S Kumar3³Janakiram M³Shaik Fayaz Ahamed²Vinoth Kumar⁴vijila S⁴Sekar S⁵Kuralmozhi R⁵Dhanaraj Baskaran¹Syed Hissar^1*Subash Babu²

• ¹National Institute of Research in Tuberculosis (ICMR), Chennai, India
• ²International Centers for Excellence in Research (ICER), Chennai, Tamil Nadu, India
• ³Tamil Nadu State AIDS Control Society, Chennai, Tamil Nadu, India
• ⁴Government Hospital of Thoracic Medicine, Chennai, Tamil Nadu, India
• ⁵Rajiv Gandhi Govt. General Hospital, Chennai, India

Background: Tuberculosis (TB) remains the primary cause of death among individuals infected with HIV, increasing the risk of contracting TB by up to 26 times. This co-infection complicates the diagnosis and treatment of TB, ultimately affecting outcomes adversely. Acute-phase proteins (APPs), markers of inflammation, are significantly elevated during infections and serve as critical indicators of inflammation resulting from infectious diseases. In this prospective study, HIVpositive individuals at antiretroviral therapy (ART) clinics were screened for latent tuberculosis infection (LTBI) before starting isoniazid (INH) prophylaxis. Initially, 101 patients were enrolled, with 71 completing a six-month follow-up on INH prophylaxis. LTBI was diagnosed using QuantiFERON-TB Gold plus, categorizing participants as HIV-positive with LTBI (n=30) and HIV-positive without LTBI (n=71). Plasma levels of alpha-2-macroglobulin (A2M), C-reactive protein (CRP), serum amyloid P (SAP), haptoglobin, ferritin, soluble transferrin receptor (sTFR), apotransferrin, hepcidin, and S100A8/A9 were assessed using multiplex and quantikine assays.At baseline, levels of A2M, CRP, SAP, ferritin, hepcidin, and S100A9 were significantly elevated in HIV-positive patients with LTBI compared to those without LTBI (A2M, p=0.005; CRP, p<0.001; SAP, p=0.0006; ferritin, p<0.001; hepcidin, p=0.001; S100A9, p=0.001). Following six months of INH prophylaxis, significant reductions in these markers were observed in both groups, suggesting a reduction in inflammation.Our findings indicate that a baseline profile of APPs can effectively reflect the inflammatory status of HIV patients with LTBI. These inflammatory markers tend to decrease following effective INH treatment, underscoring their potential utility in monitoring disease progression and treatment response in this vulnerable population.