A Novel Chemiluminescent Immunoassay for Urinary LAM Detection Improves Tuberculosis Diagnosis in HIV Cohorts

Tuberculosis (TB) is a highly prevalent opportunistic infection and a leading cause of mortality worldwide, particularly among those living with human immunodeficiency virus (HIV). Among these patients, the diagnostic accuracy of conventional TB testing is generally limited by atypical clinical manifestations, the frequent occurrence of extrapulmonary TB, challenges in obtaining sputum samples, and consistently low bacterial loads in clinical specimens. Therefore, this study assesses the diagnostic performance of a novel chemiluminescence immunoassay (CLIA) for detecting urinary lipoarabinomannan (LAM) in individuals coinfected with HIV and TB.

A prospective cohort study was conducted involving 297 people living with HIV (PLWH) recruited from Beijing Youan Hospital, Capital Medical University, China, between May 2021 and December 2024. By September 2025, when this analysis was finalized, all patients had received at least 6 months of follow-up. Of these, 76 patients had TB (34 definite cases and 42 probable cases), while 221 non-TB patients with confirmed alternative diagnoses were included as a control group. A novel double-antibody sandwich CLIA was specifically designed to detect the Mycobacterium tuberculosis LAM antigen in urine specimens. For comparative evaluation, all samples were concurrently analyzed using the commercially available Determine™ TB LAM Ag test (AlereLAM, Abbott Laboratories, USA). Investigators were blinded to the laboratory test results until the completion of enrollment, and laboratory technicians were blinded to patients' diagnoses throughout the study duration.

Receiver operating characteristic (ROC) analysis showed an area under the curve (AUC) of 0.925 at the optimal cutoff of 1.46. Median CLIA values increased in a graded manner across groups: 0.98 in the non-TB group, 1.96 in the probable TB group, and 4.46 in the definite-TB group (p < 0.001). Compared with AlereLAM, CLIA demonstrated significantly higher sensitivity (85.3% vs. 58.8%) but lower specificity (89.6% vs. 98.2%). Neither LAM-CLIA nor AlereLAM exhibited a significant association with patient cluster of differentiation (CD) 4⁺ T cell counts (p > 0.05).

CLIA-based urinary LAM detection demonstrates superior sensitivity compared with conventional lateral flow assays, providing a rapid and quantitative approach for detecting HIV-associated TB. This method has significant potential to improve early TB detection in high-risk populations, particularly where culture-based methods are unavailable.