title: Effectiveness of RHZE-FDC (fixed-dose combination) compared to RH-FDC + Z for tuberculosis treatment in Brazil: a cohort study.
abstract: BACKGROUND
  In 2009, Brazil was the sole high-burden country to use three drugs [rifampin (R), isoniazid (H) and pyrazinamide (Z)] as the standard treatment for sensitive tuberculosis, with RH in fixed-dose combination (FDC). In December 2009, the country has adopted the FDC four-drug regimen including ethambutol (E). The rationale was the expectation to reduce default and resistance rates, by increasing adherence to treatment and avoiding monotherapy. However, there is no consensus on the superior effectiveness of the RHZE-FDC regimen over RH-FDC + Z. In particular, few studies evaluated its influence on default and smear negativation rates.
  
  
  METHODS
  We conducted a historic cohort study to assess the effectiveness of RHZE-FDC for the treatment of tuberculosis in Brazil, measured by the rates of treatment default and smear negativation in the second month of treatment, using secondary data from the national information system known as SINAN-TB.
  
  
  RESULTS
  The RHZE-FDC had a protective effect against treatment default compared to RH-FDC + Z, reducing it by 14%. However, it was not possible to show an effect of the RHZE-FDC on the rate of second month smear negativation. In addition to the regimen, other well-studied individual characteristics, such as older age (over 38 years) and higher education occupation were also protective against default. Conversely, alcoholism increased the probability of defaulting. These programmatic findings suggests the benefits of RHZE-FDC over RH-FDC + Z.
  
  
  CONCLUSIONS
  Our analysis of a cohort database in a high burden country shows that compared to RH-FDC + Z, RHZE-FDC reduces the default rates, independently of other influencing individual or health service factors.
authors: National School of Public Health, Fiocruz, Rio de Janeiro, Brazil. ueleres@gmail.com.|Social Medicine Institute, Rio de Janeiro State University, Rio de Janeiro, Brazil. ueleres@gmail.com.
authors: José Ueleres
authors: JU
authors: Braga
authors: Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. atrajman@gmail.com.|Montreal Chest Institute, McGill University, Montreal, Canada. atrajman@gmail.com.
authors: Anete
authors: A
authors: Trajman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000995:Antitubercular Agents / Q000008:administration & dosage*; D001938:Brazil / Q000453:epidemiology; D015331:Cohort Studies; D004338:Drug Combinations; D004977:Ethambutol / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007538:Isoniazid / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D011718:Pyrazinamide / Q000008:administration & dosage*; D012293:Rifampin / Q000008:administration & dosage*; D016896:Treatment Outcome; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy* / Q000453:epidemiology
chemical_list: D000995:Antitubercular Agents; D004338:Drug Combinations; D011718:Pyrazinamide; D004977:Ethambutol; D007538:Isoniazid; D012293:Rifampin