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Urine lipoarabinomannan to monitor antituberculosis therapy response and predict mortality in an HIV-endemic region: a prospective cohort study
  1. Paul K Drain1,2,
  2. Lilishia Gounder3,
  3. Anneke Grobler4,
  4. Faieza Sahid5,
  5. Ingrid V Bassett1,2,
  6. Mahomed-Yunus S Moosa6
  1. 1Medical Practice Evaluation Center, Boston, Massachusetts, USA
  2. 2Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
  3. 3Department of Virology, National Health Laboratory Service, Inkosi Albert Luthuli Central Hospital, Durban, South Africa
  4. 4Centre for the AIDS Programme of Research in South Africa, Durban, South Africa
  5. 5University of Witwatersrand, Johannesburg, South Africa
  6. 6Department of Infectious Diseases, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa
  1. Correspondence to Dr Paul K Drain; pdrain{at}partners.org

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.

Design Prospective cohort.

Setting Outpatient referral clinic and tertiary hospital in South Africa.

Participants Adults (≥18 years) with ≥2 TB-related symptoms (cough, fever, weight loss, night sweats) for ≥2 weeks being initiated on anti-TB therapy.

Interventions 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.

Outcome measures 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/mm3 (IQR 89–256/mm3). 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.

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

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