Research Protocol - Effectiveness and safety of a simplified short regimen for Multidrug Resistant Tuberculosis treatment in Manzini Region, Swaziland

Abstract

Multidrug resistant tuberculosis (MDR TB) is a growing problem and few people have access to adequate diagnosis and treatment. The current recommended treatment regimen for MDR TB has a minimum of 20 months duration. Evidence from Bangladesh in 2010 showed that a 9-month short-course regimen could achieve a relapse free-cure rate of 88%. Several countries in West Africa started implementing similar regimens with similar outcomes. Evidence of effectiveness of this shortened regimen amongst HIV co-infected population is still limited. We propose an observational study to evaluate the effectiveness of a shortened course MDR TB regimen in the high HIV prevalence and high MDR TB prevalence setting of Manzini Region, Swaziland. Main objective To describe outcomes at end of treatment and relapse rate at 1 year and safety following treatment completion of a short course (9-12 month) MDR TB treatment in HIV co-infected patients in programmatic conditions in Manzini region, Swaziland. Secondary objectives 1. To describe sputum smear microscopy and culture conversion rates at 6 months and time to sputum conversion in both: HIV/MDR TB co-infected patients and MDR TB/HIV negative patients. 2. To describe outcomes at end of treatment and relapse after 1 year of treatment completion of MDR TB treatment in HIV negative patients. 3. To describe the adverse events of the treatment regimen in both: HIV/MDR TB co-infected patients and MDR TB/HIV negative patients. 4. To evaluate risk factors for unfavorable outcomes (death, lost-to-follow up and failure) and relapse as a combined cohort. 5. To describe proportion of inhA and katG mutations for H and correlation with DST for high dose at MIC 1.0 mg/ml amongst MDR TB cases and examine whether genetic mutations for H are risk factors for favorable or unfavorable outcomes (including description of outcomes 10 per baseline level of resistance to H), to increase understanding of the role of high dose H in the regimen. 6. To describe the proportion of relapse and re-infection amongst the patients developing TB at 1 year after treatment completion by genotyping. 7. To describe the correlation of smear microscopy with culture to assess the safety of a simplified monitoring with smear microscopy for MDR TB treatment. 8. To describe the rate of resistance amplification amongst patients with outcome failure.