Tuberculosis Treatment Shortening Trial

Inclusion Criteria:

• Adults, male or female, aged 18-60.
• Newly diagnosed initial episodes of pulmonary tuberculosis. Sputum smear-positive and -negative patients are eligible for enrollment. The diagnosis of tuberculosis must be confirmed by culture. Acid fast bacteria (AFB) smear positive patients found later not to have tuberculosis (TB) (i.e. those with non-tuberculous mycobacterial disease) and those without culture confirmation [at least one culture on solid media growing > 10 colonies of Mycobacterium tuberculosis (MTB) or a positive BACTEC or Mycobacteria growth indicator tube (MGIT) enriched liquid culture growing MTB] will be removed from the study.
• Chest X-ray and clinical findings consistent with tuberculosis.
• Hemoglobin greater than or equal to 8 gm/dL (greater than or equal to 5.0 mmol/L).
• Serum creatinine < 2 mg/dL (< 177 micro mol/L).
• Serum aspartate aminotransferase (AST) < 1.5 times the upper limit of normal for the testing laboratory, and serum total bilirubin < 1.3 mg/dL (22.2 micro mol/L).
• Random serum glucose less than or equal to 150 mg/dl (8.3 mmol/L).
• Ambulatory.
• Willing to provide informed consent for study participation, provide required specimens for examination, and to undergo and receive results of human immunodeficiency virus (HIV) testing.
• Willing to receive supervised anti-TB treatment.
• Completion of the required 112 doses of chemotherapy within 18 weeks of starting treatment.

Exclusion Criteria:

• Human immunodeficiency virus (HIV)-infected.
• History of prior tuberculosis or history of previous tuberculosis treatment.
• Pregnant or breastfeeding.
• Cavitary tuberculosis on initial chest X-ray (taken within 14 days of study entry).
• Exposure to person(s) with known drug resistant tuberculosis.
• Patients receiving chronic steroids or other immunosuppressive medications.
• Extra-pulmonary tuberculosis.
• Patients with drug resistant tuberculosis (resistance to isoniazid (INH), rifampicin, pyrazinamide or ethambutol).
• Professional sex worker, alcoholic and/or intravenous (IV) drug abuser.
• Silicosis or other serious chronic medical problems including diabetes mellitus or chronic renal failure.

Final determination of eligibility will be made after review of drug susceptibility testing results on an initial sputum isolate and results of all sputum cultures.

Pregnant patients may not be enrolled in the study. Patients in the 4 month arm who become pregnant during months 5 and 6 of study participation will be dropped from the study and receive an additional 2 months of treatment with INH and rifampicin.