Comparison of four Fixed Dose Combinations versus standard treatment with separate anti-TB drugs for treatment of pulmonary tuberculosis

INTERVENTION: Test arm: 4 FDC formulation (ethambutol (275 mg)/ rifampicin (150 mg)/ isoniazid (75 mg)/ pyrazinamide (400 mg) followed by 2 FDC formulation (rifampicin (150 mg)/ isoniazid (75 mg)) Control arm: Loose formulations of ethambutol (400 mg), rifampicin (450 mg), isoniazid (225 mg), pyrazinamide (400 mg) followed by loose formulations of rifampicin (150 mg), isoniazid (225 mg) and isoniazid (100 mg) CONDITION: Tuberculosis ; Infections and Infestations ; Tuberculosis PRIMARY OUTCOME: Cure rates at end of treatment (6 months) SECONDARY OUTCOME: 1. Early response rates: proportion of patients with negative culture results at 8 weeks after initiation of therapy ; 2. Proportion of patients with relapses during the 72 weeks follow up period after the end of treatment. A relapse is a patient previously treated for tuberculosis who has met the case definition of cure (as defined above) and been declared cured by a physician and who has now been diagnosed with bacteriologically positive (two positive smears and culture positive) tuberculosis. If there is discordance between smear and culture results, a clinical decision will be made regarding further management: ; 2.1. Smear positive, culture negative, and ; 2.2. Smear negative and culture positive; 3. Cure rates in HIV positive TB patients; 4. Proportion of patients with clinical deterioration of pulmonary tuberculosis with the need for hospitalisation; 5. Proportion of patients with serious adverse events any time during chemotherapy; 6. Proportion of patients with any adverse events during chemotherapy; 7. Proportion of patients completing treatment (defined as patients who achieved a total of 54 out of 56 doses in the first eight weeks of treatment and 107 out of 112 doses at a daily rate during the subsequent 16 weeks of treatment) within each group. (96% doses taken considered as completed in intensive and maintenance phases).; 8. Proportion of patients who developed multi‐drug‐resitant (MDR)‐TB INCLUSION CRITERIA: Patients with newly diagnosed pulmonary tuberculosis (with or without pleural effusion) will be admitted to the study provided they fulfill the following criteria: 1. Two sputum specimens positive for tubercle bacilli on direct smear microscopy. A patient is considered smear positive if: 1.1. 2 out of 3 consecutive sputum smears are read as positive, or 1.2. 2 out of 5 are read as positive in the event that only one of the first three smear is positive, in which case the patient will be asked for two more specimens: one morning and one spot. 2. No history of previous anti‐tuberculosis chemotherapy, or antiretroviral therapy 3. Aged 18 years and over 4. A firm home address and intent to remain there during the entire treatment and follow up period 5. Informed consent to participate in the study 6. Weight between 40.00 kg and 70.00 kg inclusive 7. Acceptance of human immunodeficiency virus (HIV) counselling and testing 8. CD4 more than