Multicentre accuracy trial of FUJIFILM SILVAMP TB LAM test in people with HIV reveals lot variability

Rationale There is an urgent need for rapid, non-sputum point-of-care diagnostics to detect tuberculosis. Objectives This prospective trial in seven high tuberculosis burden countries set out to evaluate the diagnostic accuracy of the point-of-care urine-based lipoarabinomannan assay FUJIFILM SILVAMP TB LAM (FujiLAM) among inpatient and outpatient people living with HIV. Methods Diagnostic performance of FujiLAM at point of care was assessed among adult people with HIV against a mycobacterial reference standard (sputum culture, blood culture, and Xpert Ultra from urine and sputum at enrollment, and additional sputum culture ≤7 days from enrollment), an extended mycobacterial reference standard including available non-study test results, and a composite reference standard including clinical evaluation. Measurements and Main Results Of 1624 participants enrolled, 294 (18·0%) were classified as TB positive by eMRS. Median age was 40 years, median CD4 cell count was 372 cells/ul, 52% were female and 78% were taking antiretroviral therapy at enrollment. Overall FujiLAM sensitivity was 54·8% (95% CI: 49·1–60·4), and overall specificity was 85·1% (83·1–86·9), against the extended mycobacterial reference standard. Sensitivity and specificity estimates varied between sites, ranging from 26·5% (95% CI: 17·4%–38·0%) to 83·3% (43·6%–97·0%), and 75·0 (65·0%–82·9%) to 96·5 (92·1%–98·5%), respectively. Post-hoc exploratory analysis identified significant variability in the performance of the six FujiLAM lots used in this study. Conclusions Lot variability limited interpretation of FujiLAM test performance. Although the results with the current version of FujiLAM are too variable for clinical decision-making, the lipoarabinomannan biomarker still holds promise for tuberculosis diagnostics. ### Competing Interest Statement RS, AM, CMD and MR are or were employed by FIND, the global alliance for diagnostics at the time of the study. FIND is a not-for-profit foundation that supports the evaluation of publicly prioritized tuberculosis assays and the implementation of WHO-approved (guidance and prequalification) assays using donor grants. FIND has product evaluation agreements with several private sector companies that design diagnostics for tuberculosis and other diseases. These agreements strictly define FIND's independence and neutrality with regard to these private sector companies. TB reports patents in the field of TB detection and is a shareholder of Avelo Inc. ### Clinical Trial NCT04089423 ### Funding Statement This work was funded by the Global Health Innovative Technology Fund (GHIT Grant Number G2017-207), the KfW (Grant Number 2020 60 457), Commonwealth of Australia represented by the Department of Foreign Affairs and Trade (DFAT Grant Number 70957) and the Netherlands Enterprise Agency (Grant Number PDP15CH14). Graeme Meintjes was supported by the Wellcome Trust (098316, 214321/Z/18/Z, and 203135/Z/16/Z), and the South African Research Chairs Initiative of the Department of Science and Technology and National Research Foundation (NRF) of South Africa (Grant No 64787). Peter MacPherson was funded by Wellcome (206575/Z/17/Z). This research was funded in part by the Wellcome Trust. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The ethics committees of UCT Human Research Ethics Committee, Western Cape Government Health Impact Assessment (South Africa); College of Medicine Research Support Centre (Malawi); Biomedical Research Ethics Committee, National Health Research Authority (Zambia); Infectious Disease Institute Scientific review Committee, Mulago Hospital REC, Uganda National Council for Science and Technology (Uganda); Ifakara Health Institute Scientific Committee, Tanzania Medicines and medical Devices Authority, National Institute for Medical Research (Tanzania); National Lung Hospital Ethics Committee, Ministry of Health (Viet Nam); IRB of Faculty of Medicine, Chulalongkorn University, Bangkok Metropolitan Administration Human Research Ethics Committee, Bamrasnaradura Infectious Diseases Institute (Thailand) gave ethical approval for this work. 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