title: Evaluation of a point-of-care tuberculosis test-and-treat algorithm on early mortality in people with HIV accessing antiretroviral therapy (TB Fast Track study): study protocol for a cluster randomised controlled trial.
abstract: BACKGROUND
  Early mortality for HIV-positive people starting antiretroviral therapy (ART) remains high in resource-limited settings, with tuberculosis the most important cause. Existing rapid diagnostic tests for tuberculosis lack sensitivity among HIV-positive people, and consequently, tuberculosis treatment is either delayed or started empirically (without bacteriological confirmation). We developed a management algorithm for ambulatory HIV-positive people, based on body mass index and point-of-care tests for haemoglobin and urine lipoarabinomannan (LAM), to identify those at high risk of tuberculosis and mortality. We designed a clinical trial to test whether implementation of this algorithm reduces six-month mortality among HIV-positive people with advanced immunosuppression.
  
  
  METHODS
  The TB Fast Track study is an open, pragmatic, cluster randomised superiority trial, with 24 primary health clinics randomised to implement the intervention or standard of care. Adults (aged ≥18 years) with a CD4 count of 150 cells/μL or less, who have not received any tuberculosis treatment in the last three months, or ART in the last six months, are eligible. In intervention clinics, the study algorithm is used to classify individuals as at high, medium or low probability of tuberculosis. Those classified as high probability start tuberculosis treatment immediately, followed by ART after two weeks. Medium-probability patients follow the South African guidelines for test-negative tuberculosis and are reviewed within a week, to be re-categorised as low or high probability. Low-probability patients start ART as soon as possible. The primary outcome is all-cause mortality at six months. Secondary outcomes include severe morbidity, time to ART start and cost-effectiveness.
  
  
  CONCLUSIONS
  This trial will test whether a primary care-friendly management algorithm will enable nurses to identify HIV-positive patients at the highest risk of tuberculosis, to facilitate prompt treatment and reduce early mortality. There remains an urgent need for better diagnostic tests for tuberculosis, especially for people with advanced HIV disease, which may render empirical treatment unnecessary.
  
  
  BACKGROUND
  This trial was registered with Current Controlled Trials (identifier: ISRCTN35344604 ) on 12 September 2012.
authors: Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, Keppel Street, London, WC1E 7HT, UK. katherine.fielding@lshtm.ac.uk.
authors: Katherine L
authors: KL
authors: Fielding
authors: Aurum Institute, 29 Queens Road, Johannesburg, 2041, South Africa. scharalambous@auruminstitute.org.
authors: Salome
authors: S
authors: Charalambous
authors: School of Medicine, Johns Hopkins University, 1503 E. Jefferson Street, Baltimore, Maryland, 21231, USA. choffmann@jhmi.edu.
authors: Christopher J
authors: CJ
authors: Hoffmann
authors: Technical Assistance Cluster, Foundation for Professional Development, 173 Mary Road, Pretoria, 0184, South Africa. SuzanneJ@foundation.co.za.
authors: Suzanne
authors: S
authors: Johnson
authors: Aurum Institute, 29 Queens Road, Johannesburg, 2041, South Africa. MTlali@auruminstitute.org.
authors: Mpho
authors: M
authors: Tlali
authors: School of Medicine, Johns Hopkins University, 1503 E. Jefferson Street, Baltimore, Maryland, 21231, USA. dsusan1@jhmi.edu.
authors: Susan E
authors: SE
authors: Dorman
authors: Department of Global Health and Development, London School of Hygiene & Tropical Medicine, Keppel Street, London, WC1E 7HT, UK. anna.vassall@lshtm.ac.uk.
authors: Anna
authors: A
authors: Vassall
authors: Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, Keppel Street, London, WC1E 7HT, UK. GChurchyard@auruminstitute.org.|Aurum Institute, 29 Queens Road, Johannesburg, 2041, South Africa. GChurchyard@auruminstitute.org.
authors: Gavin J
authors: GJ
authors: Churchyard
authors: Department of Clinical Research, London School of Hygiene & Tropical Medicine, Keppel Street, London, WC1E 7HT, UK. alison.grant@lshtm.ac.uk.
authors: Alison D
authors: AD
authors: Grant
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000175:diagnosis* / Q000188:drug therapy; D000328:Adult; D000465:Algorithms; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D000995:Antitubercular Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000652:urine; D015992:Body Mass Index; D002985:Clinical Protocols; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D008070:Lipopolysaccharides / Q000652:urine; D014376:Tuberculosis / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy
chemical_list: D044966:Anti-Retroviral Agents; D000995:Antitubercular Agents; D015415:Biomarkers; D006454:Hemoglobins; D008070:Lipopolysaccharides; C050016:lipoarabinomannan