The Diagnostic Accuracy of Urine-Based Xpert MTB/RIF in HIV-Infected Hospitalized Patients Who Are Smear- Negative or Sputum Scarce

Background: Hospitals in sub-Saharan Africa are inundated with HIV-infected patients and tuberculosis (TB) is the commonest opportunistic infection in this sub-group. Up to one third of TB-HIV co-infected patients fail to produce a sputum sample (sputum scarce) and diagnosis is thus often delayed or missed. We investigated the sensitivity of urine-based methods (Xpert MTB/RIF, LAM strip test and LAM ELISA) in such patients. Methodology/Principal Findings: 281 HIV-infected hospitalised patients with clinically suspected TB provided a spot urine sample. The reference standard was culture positivity for Mycobacterium tuberculosis on $1 sputum or extra-pulmonary sample. MTB/RIF was performed using 1 ml of both unprocessed and, when possible, concentrated urine. Each unconcentrated urine sample was also tested using the Clearview LAM ELISA and Alere LAM strip test. 42 % (116/242) of patients had culture-proven TB. 18 % (20/54) were sputum scarce. In sputum-scarce patients, the sensitivity of urine MTB/RIF and LAM ELISA was 40 % (95%CI: 22–61) and 60 % (95%CI: 39–78), respectively. Urine MTB/RIF specificity was 98 % (95%CI: 95–100). Combined sensitivity of urine LAM ELISA and MTB/RIF was better than MTB/RIF alone [MTB/RIF and LAM: 70% (95%CI: 48–85) vs. MTB/RIF: 40 % (95%CI: 22–61), p = 0.03]. Significant predictors of urine MTB/RIF positivity were CD4,50 cells/ml (p = 0.001), elevated protein-to-creatinine ratio (p,0.001) and LAM ELISA positivity (p,0.001). Urine centrifugation and pelleting significantly increased the sensitivity of MTB/RIF over unprocessed urine in paired samples [42 % (95%CI: 26