Lateral Flow Urine Lipoarabinomannan Assay for Diagnosis of Active Tuberculosis in Adults With Human Immunodeficiency Virus Infection: A Prospective Cohort Study

Abstract

Detection of mycobacterial lipoarabinomannan antigen in urine has emerged as a potential point-of-care test for diagnosis of tuberculosis. This study aimed to evaluate the accuracy of the lateral flow urine lipoarabinomannan (LF-LAM) assay for diagnosis of active tuberculosis among Thai adults with advanced human immunodeficiency virus (HIV) infection. HIV-infected adult patients with CD4 cell counts ≤200/μL and symptoms suggestive of active tuberculosis were prospectively recruited from both inpatient and outpatient settings at Siriraj Hospital and Chonburi Hospital in Thailand during the study period from December 2015 to March 2017. Freshly collected urine samples were applied to the Alere Determine TB LAM Ag test strip using a grade 1 cutoff, according to the manufacturer’s grading system. The diagnostic accuracy of the LF-LAM test was assessed against a microbiological reference standard (definite tuberculosis) or a composite reference standard (definite and probable tuberculosis). Of the 280 patients who were included, 72 (25.7%) had definite and 65 (23.2%) had probable tuberculosis. Among patients with definite tuberculosis, the LF-LAM test yielded a sensitivity of 75.0% and a specificity of 76.0%. It had the highest sensitivity (90.5%) in HIV-infected patients with CD4 cell counts <50/μL. It yielded a lower sensitivity (61.3%) but a higher specificity (86.0%) when compared with the composite reference standard. Among the 20 patients (14%) with false-positive results, strong band intensity was observed mostly in Mycobacterium avium complex infections. An incremental sensitivity of 11% was observed with use of acid-fast bacilli sputum smear or LF-LAM testing, compared with LF-LAM testing alone. The LF-LAM test performed well in the diagnosis of active tuberculosis in selected patients with more advanced tuberculosis and coexisting HIV disease.