Comparative performance of urinary lipoarabinomannan assays and Xpert MTB/RIF in HIV-infected individuals

Background: Xpert MTB/RIF ('Xpert') and urinary lipoarabinomannan (LAM) assays offer rapid tuberculosis (TB) diagnosis, but have suboptimal sensitivity when used individually in HIV-positive patients. The yield of these tests used in combination for the diagnosis of active TB among HIV-infected TB suspects is unknown. Design: Study of comparative diagnostic accuracy nested into a prospective study of HIV-infected individuals with signs and/or symptoms of TB in Uganda. Methods: Xpert testing of archived sputum was conducted for culture-confirmed TB cases and TB suspects in whom a diagnosis of TB was excluded. Additional testing included sputum smear microscopy, sputum culture (solid and liquid media), mycobacterial blood culture, and urinary testing for LAM using a lateral flow test ('LF-LAM') and an enzyme-linked immunosorbance assay ('ELISA-LAM'). Results: Among 103 participants with culture-confirmed TB, sensitivity of Xpert was 76% (95% confidence interval, CI 0.66-0.84), and was superior to that of LF-LAM (49%, 95% CI 0.39-0.59, P<0.001). Specificity was greater than 97% for both tests among 105 individuals without TB. The combination of smear microscopy and LF-LAM identified 67% (95% CI 0.57-0.76) of culture-confirmed TB cases and approached sensitivity of Xpert testing alone (P=0.15). The sensitivity of the combination of Xpert and LF-LAM was 85% (88/103 95% CI 0.77-0.92), which was superior to either test alone (P<0.05) and approached sensitivity of sputum liquid culture testing (94%, 95% CI 0.88-0.98, P=0.17). Conclusion: Sputum Xpert and urinary LAM assays were complementary for the diagnosis of active TB in HIV-infected patients, and sensitivity of the combination of these tests was superior to that of either test alone.