Urinary lipoarabinomannan as predictor for the tuberculosis immune reconstitution inflammatory syndrome

BACKGROUND: Upon initiation of antiretroviral therapy (ART), 15.7% (95%CI: 9.7%-24.5%) of tuberculosis (TB)-HIV co-infected individuals experience paradoxical worsening of their clinical status with exuberant inflammation consistent with Immune Reconstitution Inflammatory Syndrome (IRIS). We investigated whether a positive urinary TB lipoarabinomannan (LAM) antigen ELISA-test prior to ART initiation was associated with development of paradoxical TB-IRIS. METHODS: In a prospective observational cohort in Mulago Hospital, Kampala, Uganda, we measured pre-ART urinary LAM concentrations in HIV-infected patients on TB treatment. Patients who developed TB-IRIS (according to the International Network for the Study of HIV-associated IRIS (INSHI) case-definition) were compared to patients who remained IRIS free for at least 3 months. RESULTS: Twenty-six individuals with TB-IRIS and 64 without IRIS were included in the analysis. The median time to TB-IRIS was 14 days (IQR: 11-14). Univariate analysis showed that a positive pre-ART urinary LAM test (OR: 4.6 [95%CI: 1.5-13.8], p=0.006) and a CD4 count <50 cells/ml (OR: 21 [95%CI: 2.6-169.4], p=0.004) were associated with an increased risk of TB-IRIS. In multivariate analysis only a baseline CD4 T-cell count <50 cells/ml was predictive of IRIS (p<0.004). Sensitivity and specificity of a positive pre-ART urinary LAM test to diagnose IRIS was 80.8% (95%CI: 60.6-93.4) and 52.4% (95%CI: 39.4-65.1), respectively. CONCLUSION: If CD4 T-cell count testing is available, a pre-HAART urinary LAM test has no added value to predict TB IRIS. When CD4 T-cell count is not available, a positive LAM test could identify patients at increased risk of TB IRIS.