Acute-phase proteins as biomarkers of inflammation in HIV patients with latent tuberculosis: a prospective study

Abstract

Introduction: 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.

Methods: In this prospective study, HIV-positive 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).

Results: 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.

Discussion: 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.

Keywords: HIV; LTBI; acute-phase proteins; biomarkers; isoniazid preventive treatment (IPT).

Figure 1

Elevated acute phase proteins in HIV patients with LTBI. Plasma levels of acute phase proteins (APPs) were measured in HIV patients with latent tuberculosis infection (LTBI) (n = 30) and HIV patients without LTBI (n = 71) using multiplex and quantitative ELISA kit. Each circle represents an individual, with p values calculated using the Mann–Whitney test with Holm’s correction for multiple comparisons.

Figure 2

Diminished APPs levels after IPT in HIV patients. The plasma levels of APPs were measured at baseline (pre) and 6 months following isoniazid preventive treatment (IPT) in (A) HIV patients with LTBI (n = 22) and (B) HIV patients without LTBI (n = 52). Line graphs represent individual trajectories, with p values calculated using the Wilcoxon signed rank test.

Figure 3

Profiling of APPs as immune markers in HIV patients with and without LTBI. Hierarchical cluster analysis was conducted to examine immune markers that differed statistically between HIV patients with and without LTBI. (A) Comparison between HIV patients with and without LTBI, (B) HIV patients with LTBI, and HIV patients without LTBI during pre and post IPT. Univariate analysis enabled the separation of groups based on individual levels of each subject. Data were log10 transformed and z-score normalized.