Using Urine Lipoarabinomannan (LAM) in Practice: The Incremental Yield of Urine LAM and Xpert MTB/RIF Testing in Hospitalized HIV-Infected Patients
CHEST(2017)
Abstract
SESSION TITLE: Tuberculosis and Other Pulmonary Infections SESSION TYPE: Original Investigation Slide PRESENTED ON: Monday, October 30, 2017 at 04:30 PM - 05:30 PM PURPOSE: In sub-Saharan Africa, TB and HIV co-infection is associated with a high mortality. The Xpert MTB/RIF test is an automated assay that permits rapid identification of Mycobacterium TB in the sputum. However, it does not perform as well in HIV-positive patients, who often have smear negative disease. The Alere DetermineTM TB LAM Ag lateral flow strip test is a bedside urine TB test that identifies lipoarabinomannan (LAM), a glycolipid component of the mycobacterial cell wall. It has established utility in HIV patients with advanced immunosuppression. We sought to determine the benefit of combining sputum Xpert MTB/RIF and urine LAM testing as well as the incremental yield of doing sequential testing in a large cohort of hospitalized HIV-positive patients. METHODS: This study represents a post hoc sub-group analysis of data from a randomized multicenter study. We included patients randomized to the LAM arm and in whom both Xpert MTB/RIF and sputum culture results were available. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of each diagnostic test was calculated. Diagnostic utility of urine LAM with Xpert MTB/RIF testing vs. Xpert MTB/RIF testing alone was compared, and the incremental yield of urine LAM in the diagnosis of TB was estimated. The reference standard for the diagnosis of TB was sputum culture positive for TB. RESULTS: Of 1257 patients randomized to the LAM study arm, 561 patients were selected for analysis. Urine LAM was found to have a sensitivity of 38.1% (95% CI 30.9 - 45.7%) and a specificity of 88.1% (95% CI 84.3 - 91.1%). Xpert MTB/RIF had a sensitivity of 75.0% (95% CI 67.9 - 81.2%) and a specificity of 95.1% (95% CI 92.4 - 97.0%). We compared three diagnostic strategies: using both urine LAM and Xpert MTB/RIF testing for all patients suspected of TB; using urine LAM only in those found to have a negative Xpert MTB/RIF; and using Xpert MTB/RIF in only those who had negative urine LAM results. All diagnostic strategies had a sensitivity of 78.4% (95% CI 71.6 - 84.2%), specificity of 84.6% (95% CI 80.7 - 88.1%), PPV of 70.1% (95% CI 63.1-76.4%), and NPV of 89.6% (95% CI 86.0 - 92.5%). Compared to a diagnostic strategy using Xpert MTB/RIF alone, there was a significant decrease in specificity (10.4% difference, 95% CI 6.2 - 14.6%, p<0.0001) and PPV (17.3% difference, 95% CI 9.1 - 25.7%, p=0.001), and no significant change in sensitivity (-3.4% difference, 95% CI -12.2 - 5.4%, one-way p=0.22) or NPV (-0.3%, 95% CI -4.6 - 4.0%, one-way p=0.45) when urine LAM is performed in addition to Xpert MTB/RIF. The incremental yield of adding urine LAM after Xpert MTB/RIF was 4.5% (6 urine LAM positive/132 Xpert MTB/RIF positive). CONCLUSIONS: Our study shows that as a stand-alone test, Xpert MTB/RIF is superior to urine LAM. However, there is a modest incremental benefit in adding urine LAM testing to diagnose TB in this population. CLINICAL IMPLICATIONS: There may be a modest benefit in using urine LAM in addition to Xpert MTB/RIF testing in hospitalized HIV patients, in whom a diagnosis of TB is often missed and can have fatal consequences. Future studies should examine the diagnostic accuracy of urine LAM in patients who are unable to generate sputum for testing. DISCLOSURE: The following authors have nothing to disclose: Natasha Sabur, Aliasgar Esmail, Mantaj Brar, Keertan Dheda No Product/Research Disclosure Information
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