Lateral flow urine lipoarabinomannan assay for detecting active tuberculosis in people living with HIV

Background The lateral flow urine lipoarabinomannan (LF-LAM) assay Alere Determine™ TB LAM Ag is recommended by the World Health Organization (WHO) to help detect active tuberculosis in HIV-positive people with severe HIV disease. This review update asks the question, "does new evidence justify the use of LF-LAM in a broader group of people?”, and is part of the WHO process for updating guidance on the use of LF-LAM. Objectives To assess the accuracy of LF-LAM for the diagnosis of active tuberculosis among HIV-positive adults with signs and symptoms of tuberculosis (symptomatic participants) and among HIV-positive adults irrespective of signs and symptoms of tuberculosis (unselected participants not assessed for tuberculosis signs and symptoms). The proposed role for LF-LAM is as an add on to clinical judgement and with other tests to assist in diagnosing tuberculosis. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register; MEDLINE, Embase, Science Citation Index, Web of Science, Latin American Caribbean Health Sciences Literature, Scopus, the WHO International Clinical Trials Registry Platform, the International Standard Randomized Controlled Trial Number Registry, and ProQuest, without language restriction to 11 May 2018. Selection criteria Randomized trials, cross-sectional, and observational cohort studies that evaluated LF-LAM for active tuberculosis (pulmonary and extra-pulmonary) in HIV-positive adults. We included studies that used the manufacturer's recommended threshold for test positivity, either the updated reference card with four bands (grade 1 of 4) or the corresponding prior reference card grade with five bands (grade 2 of 5). The reference standard was culture or nucleic acid amplification test from any body site (microbiological). We considered a higher quality reference standard to be one in which two or more specimen types were evaluated for tuberculosis diagnosis and a lower quality reference standard to be one in which only one specimen type was evaluated. Data collection and analysis Two review authors independently extracted data using a standardized form and REDCap electronic data capture tools. We appraised the quality of studies using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool and performed meta-analyses to estimate pooled sensitivity and specificity using a bivariate random-effects model and a Bayesian approach. We analyzed studies enrolling strictly symptomatic participants separately from those enrolling unselected participants. We investigated pre-defined sources of heterogeneity including the influence of CD4 count and clinical setting on the accuracy estimates. We assessed the certainty of the evidence using the GRADE approach. Main results We included 15 unique studies (nine new studies and six studies from the original review that met the inclusion criteria): eight studies among symptomatic adults and seven studies among unselected adults. All studies were conducted in low-or middle-income countries. Risk of bias was high in the patient selection and reference standard domains, mainly because studies excluded participants unable to produce sputum and used a lower quality reference standard.