An Optimal Diagnostic Strategy for Tuberculosis in Hospitalized HIV-Infected Patients Using GeneXpert MTB/RIF and Alere Determine TB LAM Ag

ABSTRACT The diagnosis of tuberculosis (TB) in HIV-infected patients is challenging. Both a urinary lipoarabinomannan (LAM) test (Alere TB LAM) and GeneXpert-MTB/RIF (Xpert) are useful for the diagnosis of TB. However, how to optimally integrate Xpert and LAM tests into clinical practice algorithms remain unclear. We performed a post hoc analysis of 561 HIV-infected sputum-expectorating patients (median CD4 count of 130 cells/ml) from a previously published randomized controlled trial evaluating the LAM test in hospitalized HIV-infected patients with suspected TB. We evaluated 5 different diagnostic strategies using sputum culture as a reference standard (Xpert alone, LAM alone, sequential Xpert followed by LAM and vice versa [LAM in Xpert-negative patients and Xpert in LAM-negative patients], and both tests concurrently [LAM + Xpert]). A cost-consequence analysis was performed. Strategy-specific sensitivity and specificity, using culture as a reference, were similar with the Xpert-only and sequential and concurrent strategies. However, when any positive TB-specific test was used as a reference, the incremental yield of LAM over Xpert was 29.6% (45/152) and that of Xpert over LAM was 75% (84/11). The incremental yield of LAM increased with decreasing CD4 count. The costs per TB case diagnosed were similar for the sequential and concurrent strategies ($1,617 to $1,626). In sputum-expectorating hospitalized patients with advanced HIV and access to both tests, concurrent testing with Xpert and LAM may be the best strategy for diagnosing TB. These data inform clinical practice in settings where TB and HIV are endemic.