Plasma Profiles of Inflammatory Markers Associated With Active Tuberculosis in Antiretroviral Therapy-Naive Human Immunodeficiency Virus-Positive Individuals

Abstract

Background

Diagnosis of tuberculosis (TB) in human immunodeficiency virus (HIV)-coinfected individuals is challenging. We hypothesized that combinations of inflammatory markers could facilitate identification of active TB in HIV-positive individuals.

Methods

Participants were HIV-positive, treatment-naive adults systematically investigated for TB at Ethiopian health centers. Plasma samples from 130 subjects with TB (HIV ⁺/TB ⁺) and 130 subjects without TB (HIV ⁺/TB ⁻) were tested for concentration of the following markers: CCL5, C-reactive protein (CRP), interleukin (IL)-6, IL12-p70, IL-18, IL-27, interferon-γ-induced protein-10 (IP-10), procalcitonin (PCT), and soluble urokinase-type plasminogen activator receptor (suPAR). Analyzed markers were then assessed, either individually or in combination, with regard to infection status, CD4 cell count, and HIV ribonucleic acid (RNA) levels.

Results

The HIV ⁺/TB ⁺ subjects had higher levels of all markers, except IL12p70, compared with HIV ⁺/TB ⁻ subjects. The CRP showed the best performance for TB identification (median 27.9 vs 1.8 mg/L for HIV ⁺/TB ⁺ and HIV ⁺/TB ⁻, respectively; area under the curve [AUC]: 0.80). Performance was increased when CRP was combined with suPAR analysis (AUC, 0.83 [0.93 for subjects with CD4 cell count <200 cells/mm ³]). Irrespective of TB status, IP-10 concentrations correlated with HIV RNA levels, and both IP-10 and IL-18 were inversely correlated to CD4 cell counts.

Conclusions

Although CRP showed the best single marker discriminatory potential, combining CRP and suPAR analyses increased performance for TB identification.