Effectiveness of RHZE-FDC (fixed-dose combination) compared to RH-FDC + Z for tuberculosis treatment in Brazil: a cohort study

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. CONCLUSION 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.