1. This randomized controlled trial of a urine-based point-of-care lipoarabinomannan assay (LAM) to detect tuberculosis infection in HIV-positive patients resulted in reduced mortality at 8 weeks in those tested with LAM plus routine diagnostic tests compared to routine tests alone.
2. LAM testing also reduced mortality due to more patients being initiated for tuberculosis treatment in the LAM group compared to the no LAM group.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Tuberculosis co-infection in HIV-positive patients results in high mortality due to increased systemic disease as a result of progressive immunosuppression associated with more severe HIV. However, tuberculosis is difficult to diagnose in HIV-positive patients due to more frequent presentations with extra-pulmonary systemic disease, inability to produce sufficient sputum for samples, or low bacterial loads in bodily fluid samples. This is a problem especially in countries endemic in HIV and tuberculosis with the need for an affordable point-of-care test. This study assessed a urine-based point-of-care lipoarabinomannan assay (LAM) to detect lipoarabinomannan, a glycolipid antigen of Mycobacterium tuberculosis cell walls, and conducted a randomized trial of patients at ten hospitals in Africa to receive either routine diagnostic tests plus LAM or routine tests alone. Participants were followed to observe for all-cause mortality at 8 weeks.
Nearly one quarter of patients overall died by 8 weeks in the study, with 4% fewer deaths in the LAM group than the no LAM group. Additionally, the LAM group was associated with a 17% relative risk reduction. More patients were also treated for tuberculosis in the LAM group compared to the no LAM group. There were no adverse effects associated with LAM testing. This study was strengthened by the use of an assay with high sensitivity in ill patients with low CD4 cell counts, but was limited in that many patients did not meet inclusion criteria because testing was not available 24 hours per day and some patients already were started on treatment prior to screening.
In-Depth [randomized controlled trial]: This pragmatic, randomized, parallel-group, multicenter trial was conducted at ten hospitals in Africa between January 1, 2013 and October 2, 2014. Participants aged 18 years or older diagnosed with HIV, presenting with at least one symptom of tuberculosis (fever, cough, night sweats, or self-reported weight loss), and requiring hospital admission were included in the study. 1,257 patients were randomized to the LAM plus routine tests (smear microscopy, Xpert-MTB/RIF assay, and culture) group and 1,271 to the routine test group. The primary outcome was all-cause mortality at 8 weeks after randomization.
Overall all-cause mortality occurred in 578 (23%) of 2,528 patients, including 261 (21%) in the LAM group and 317 (25%) in the no LAM group, resulting in an absolute reduction of 4% (95% CI 1-7). The risk ratio adjusted for country was 0.83 (95% CI 0.73-0.96, p=0.012), resulting in a relative risk reduction of 17% (95% CI 4-28). There were also less deaths per 100 person years in the LAM group vs. no LAM group (159 vs. 196; hazard ratio adjusted for country 0.82 [95% CI 0.70-0.96], p=0.0145). Additionally, more patients were treated for tuberculosis in the LAM group compared to the no LAM group (648; 52% vs. 598; 47%; p=0.024).
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