Detection of lipoarabinomannan (LAM) in urine is indicative of disseminated TB with renal involvement in patients living with HIV and advanced immunodeficiency: evidence and implications

TB is the leading cause of HIV/AIDS-related deaths globally. New diagnostic tools are urgently needed to avert deaths from undiagnosed HIV-associated TB. Although simple assays that detect lipoarabinomannan (LAM) in urine have been commercially available for years, their specific role and utility were initially misunderstood, such that they have been slower to emerge from the diagnostics pipeline than otherwise might have been expected. In this article, we review and explain how urine-LAM assays should be understood as diagnostics for disseminated TB in HIV-positive patients with advanced immunodeficiency, in whom haematogenous TB dissemination to the kidneys serves as the primary mechanism by which LAM enters the urine. These insights are critical for the appropriate design of studies to evaluate these assays and to understand how they might be most usefully implemented. This understanding also supports the 2015 WHO recommendations on the restricted use of these assays in sick HIV-positive patients with advanced immunodeficiency.