title: Urine lipoarabinomannan to monitor antituberculosis therapy response and predict mortality in an HIV-endemic region: a prospective cohort study.
abstract: OBJECTIVE
  To determine if urinary lipoarabinomannan (LAM) may serve as a biomarker to monitor antituberculosis (TB) therapy response, and whether LAM results before and after treatment are predictive of patient outcomes.
  
  
  METHODS
  Prospective cohort.
  
  
  METHODS
  Outpatient referral clinic and tertiary hospital in South Africa.
  
  
  METHODS
  Adults (≥18 years) with ≥2 TB-related symptoms (cough, fever, weight loss, night sweats) for ≥2 weeks being initiated on anti-TB therapy.
  
  
  METHODS
  On enrolment, we obtained urine and nebulised sputum specimens, offered HIV testing and started participants on anti-TB therapy for ≥6 months. We collected urine samples after the 2-month intensive treatment phase and at the completion of anti-TB therapy. Positive LAM results were graded from 1 (low) to 5 (high). Participants were followed for >3 years.
  
  
  METHODS
  The primary outcome was change in urine LAM results during anti-TB therapy. The secondary outcome was all-cause mortality.
  
  
  RESULTS
  Among 90 participants, 57 (63%) had culture-confirmed pulmonary TB. Among the 88 participants tested, 82 (93%) were HIV-infected with median CD4 168/mm(3) (IQR 89-256/mm(3)). During anti-TB therapy, the percentage of LAM-positive participants decreased from baseline to 2 months (32% to 16%), and from baseline to 6-months (32% to 10%) (p values <0.005). In multivariate longitudinal analyses, urine LAM positivity and grade decreased among those with culture-confirmed pulmonary TB (p<0.0001), and had no change in sputum culture-negative participants. At the 2-month visit, participants with positive laboratory-based LAM or rapid LAM with ≥2+ grade had a significantly greater risk of mortality. In analyses adjusted for age, sex, baseline Karnofsky score and HIV status, participants with a rapid LAM ≥2+ grade after 2 months of anti-TB therapy had a 5.6-fold (95% CI 1.2 to 25.2) greater risk of mortality.
  
  
  CONCLUSIONS
  Rapid urine LAM testing may be a valuable tool to monitor anti-TB therapy response and to assess prognosis of patients being treated for pulmonary TB in HIV-endemic regions.
authors: Medical Practice Evaluation Center, Boston, Massachusetts, USA Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors: Paul K
authors: PK
authors: Drain
authors: Department of Virology, National Health Laboratory Service, Inkosi Albert Luthuli Central Hospital, Durban, South Africa.
authors: Lilishia
authors: L
authors: Gounder
authors: Centre for the AIDS Programme of Research in South Africa, Durban, South Africa.
authors: Anneke
authors: A
authors: Grobler
authors: University of Witwatersrand, Johannesburg, South Africa.
authors: Faieza
authors: F
authors: Sahid
authors: Medical Practice Evaluation Center, Boston, Massachusetts, USA Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors: Ingrid V
authors: IV
authors: Bassett
authors: Department of Infectious Diseases, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.
authors: Mahomed-Yunus S
authors: MY
authors: Moosa
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000652:urine; D018791:CD4 Lymphocyte Count; D019353:Endemic Diseases; D005260:Female; D006678:HIV; D015658:HIV Infections / Q000150:complications* / Q000453:epidemiology; D006801:Humans; D008070:Lipopolysaccharides / Q000652:urine*; D008137:Longitudinal Studies; D008297:Male; D008403:Mass Screening; D008875:Middle Aged; D008991:Monitoring, Physiologic / Q000379:methods*; D015999:Multivariate Analysis; D009169:Mycobacterium tuberculosis; D063868:Patient Outcome Assessment; D011446:Prospective Studies; D013019:South Africa / Q000453:epidemiology; D013183:Sputum; D014397:Tuberculosis, Pulmonary / Q000150:complications / Q000188:drug therapy / Q000401:mortality / Q000652:urine*
chemical_list: D000995:Antitubercular Agents; D015415:Biomarkers; D008070:Lipopolysaccharides; C050016:lipoarabinomannan