A Trial of Stratified Patient-Centered Treatment Regimens for Active TB (SPECTRA-TB)

Inclusion Criteria: * Has pulmonary tuberculosis (TB) that is likely to respond to standard TB medicines (drug-susceptible TB), based on sputum testing done within 7 days before entering the study. The test must show Mycobacterium tuberculosis is present, with no rifamycin resistance detected and no known resistance to isoniazid or fluoroquinolones. * Has a SPECTRA-TB risk score and risk group assigned during screening using the study-specific calculator. * Has a Karnofsky performance score of 50 or higher within 30 days before entering the study. * Has documented HIV-1 status (either with HIV or without HIV) based on acceptable testing. * If living with HIV, has a CD4+ cell count of at least 50 cells/mm3 within 60 days before study entry. * If living with HIV, is currently receiving or plans to start an efavirenz-based or dolutegravir-based antiretroviral therapy regimen by study week 8. * Has laboratory test results within 7 days before study entry that meet all of the following: * alanine aminotransferase (ALT) no more than 3 times the upper limit of normal * total bilirubin no more than 2.5 times the upper limit of normal * creatinine no more than 2 times the upper limit of normal * potassium between 3.5 and 5.5 mEq/L * absolute neutrophil count at least 1000/mm3 * hemoglobin at least 7.0 g/dL * platelet count at least 100,000/mm3 * If able to become pregnant, has a negative blood or urine pregnancy test within 7 days before study entry. * If able to become pregnant and sexually active in a way that could lead to pregnancy, agrees not to try to become pregnant and agrees to use at least 1 reliable non-hormonal birth control method during study treatment and for 30 days after stopping study drugs. Acceptable methods include: * condoms * intrauterine device (IUD) or intrauterine system (IUS) * cervical cap with spermicide * diaphragm with spermicide * If not able to become pregnant, has a history or documentation of menopause, hysterectomy, bilateral removal of the ovaries, or bilateral tubal ligation. * Has a verifiable address or place of residence and is willing to tell the study team about any change of address during treatment and follow-up. * Is willing and able to give informed consent, or assent with permission from a parent or legal guardian if required. Exclusion Criteria: * TB bacteria are known to be resistant to 1 or more of the following medicines: rifampin, isoniazid, pyrazinamide, ethambutol, or fluoroquinolones. * Received more than 5 days of treatment for active TB within the 24 weeks before study entry. * Received more than 5 days of treatment within the 30 days before study entry with certain TB medicines or related antibiotics, including isoniazid, rifampin, rifapentine, ethambutol, moxifloxacin, pyrazinamide, aminoglycosides, fluoroquinolones, linezolid, bedaquiline, pretomanid, and other specified anti-TB drugs. * Has suspected or confirmed TB involving the brain or central nervous system, bones, joints, heart lining (pericardium), or miliary TB. * Has a past history of suspected or confirmed drug-resistant TB of any type. * Is currently pregnant or breastfeeding. * Cannot take medicines by mouth. * Has an HIV/AIDS-related opportunistic infection at study entry. * Has acute or chronic hepatitis B, unless the hepatitis B infection has cleared. * Has acute or chronic hepatitis C, unless the hepatitis C infection has cleared or has been successfully treated. * Has alcohol-related liver disease. * Has liver cirrhosis. * Has a history of aortic aneurysm or aortic dissection. * Has a known history of long QT syndrome, a first-degree relative with long QT syndrome, or a screening ECG showing QTcF greater than 470 ms that does not correct with treatment of contributing factors. * Is taking other medicines that can prolong the QT interval and cannot safely switch to an alternative medicine. * Has a known history of acute intermittent porphyria. * Weighs less than 30 kg. * Is currently using, or is expected to need within 24 weeks after enrollment, 1 or more medicines that are not allowed during the study. * Has a known allergy, sensitivity, or hypersensitivity to any of the study drugs or their ingredients. * Has active drug or alcohol use, dependence, mental illness, or another serious infection that, in the opinion of the site investigator, could make it hard to follow the study requirements. * Is currently taking part in another interventional clinical trial.