title: Urinary lipoarabinomannan as predictor for the tuberculosis immune reconstitution inflammatory syndrome.
abstract: BACKGROUND
  Upon initiation of antiretroviral therapy (ART), 15.7% [95% confidence interval (CI): 9.7% to 24.5%] of tuberculosis (TB)-HIV-coinfected 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 enzyme-linked immunosorbent assay test before 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 case definition) were compared with 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 (interquartile range: 11-14 days). Univariate analysis showed that a positive pre-ART urinary LAM test [OR: 4.6 (95% CI: 1.5 to 13.8), P = 0.006] and a CD4 count <50 cells/mL [OR: 21 (95% CI: 2.6 to 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 were 80.8% (95% CI: 60.6 to 93.4) and 52.4% (95% CI: 39.4 to 65.1), respectively.
  
  
  CONCLUSIONS
  If CD4 T-cell count testing is available, a pre-highly active antiretroviral therapy 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.
authors.affiliation: Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium. aconesa@itg.be
authors.forename: Anali
authors.initials: A
authors.lastname: Conesa-Botella
authors.forename: Marguerite Massinga
authors.initials: MM
authors.lastname: Loembé
authors.forename: Yukari C
authors.initials: YC
authors.lastname: Manabe
authors.forename: William
authors.initials: W
authors.lastname: Worodria
authors.forename: Doreen
authors.initials: D
authors.lastname: Mazakpwe
authors.forename: Kenneth
authors.initials: K
authors.lastname: Luzinda
authors.forename: Harriet
authors.initials: H
authors.lastname: Mayanja-Kizza
authors.forename: Mitra
authors.initials: M
authors.lastname: Miri
authors.forename: Olive
authors.initials: O
authors.lastname: Mbabazi
authors.forename: Olivier
authors.initials: O
authors.lastname: Koole
authors.forename: Luc
authors.initials: L
authors.lastname: Kestens
authors.forename: Robert
authors.initials: R
authors.lastname: Colebunders
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D000995:Antitubercular Agents / Q000627:therapeutic use*; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D054019:Immune Reconstitution Inflammatory Syndrome / Q000209:etiology* / Q000652:urine; D008070:Lipopolysaccharides / Q000652:urine*; D008297:Male; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012307:Risk Factors; D014376:Tuberculosis / Q000150:complications* / Q000188:drug therapy*; D014454:Uganda
chemical_list: D019380:Anti-HIV Agents; D000995:Antitubercular Agents; D008070:Lipopolysaccharides; C050016:lipoarabinomannan