Inclusion Criteria:

• 1. Pulmonary tuberculosis with or without suspected or proven concomitant extrapulmonary tuberculosis outside the central nervous system or bones
• 2. Acid-fast bacilli (AFB) seen in an expectorated sputum specimen at least 1+ or positive GeneXpert (or GeneXpert Ultra) for M. tuberculosis, with semiquantitative results of "medium" or "high".
• 3. Age ≥12 years
• 4. Documentation of negative HIV status within the past 3 months prior to enrollment or documentation confirming HIV infection.
• 5. For participants with HIV:
• 1. current use of dolutegravir-based ART (Anti Retroviral Therapy), or ability and willingness to start or transition to a dolutegravir-based antiretroviral therapy regimen
• 2. CD4 T cell count greater than or equal to 100 cells/mm3 based on testing performed at or within 30 days prior to study enrollment
• 6. Written informed consent/assent
• 7. Karnofsky score of at least 60 ("requiring some help, can take care of most personal requirements")
• 8. A verifiable address or residence location that is readily accessible for visiting, and willingness to inform the study team of any change of address during the treatment and follow-up period.
• 9. For all women who have not undergone a surgical sterilization procedure or who do not meet the study definition of post-menopausal, a negative pregnancy test at or within seven (7) days prior to screening
• 10. For all individuals of child-bearing potential who are not surgically sterilized, agreement to practice a reliable method of contraception (barrier method or non-hormonal intrauterine device) or abstain from sexual activity that could lead to pregnancy while receiving study drug treatment and for 30 days after stopping study treatment

Exclusion Criteria:

• 1. Pregnant or breast-feeding
• 2. More than 5 days of tuberculosis treatment in the previous 6 months
• 3. Previous treatment with any drug or combination of drugs known to have activity against M. tuberculosis (e.g., isoniazid, rifamycins, pyrazinamide, ethambutol, fluoroquinolones, etc.) for more than five days in the thirty days prior to enrollment
• 4. Unable to take oral medications
• 5. Hypersensitivity or previous intolerance to any of the study drugs
• 6. Current or planned use of medications that have unacceptable drug-drug interactions with any of the study drugs during study treatment
• 7. Suspected or proven central nervous system tuberculosis
• 8. Suspected or proven bone tuberculosis
• 9. Screening ECG with QTcF \>450 for men or \>470 for women (Note: in case of hypokalemia or hypomagnesemia, ECG can be repeated following electrolyte supplementation)
• 10. Clinically significant ECG abnormality in the opinion of the site investigator, including but not limited to second or third degree atrioventricular (AV) block, prolongation of the QRS complex over 120 ms (in both male and female participants), or clinically important arrhythmia
• 11. Current clinically relevant cardiovascular disorder in the opinion of the site investigator, including but not limited to heart failure, coronary heart disease, arrhythmia, or tachyarrhythmia
• 12. Known family history of Long QT Syndrome in a first-degree relative (i.e., parent, offspring, or sibling)
• 13. History of aortic aneurysm or dissection
• 14. Hepatic cirrhosis or other serious liver disease
• 15. Other medical conditions, that, in the investigator's judgment, make study participation not in the individual's best interest.
• 16. Laboratory parameters done at or within 14 days prior to screening:
• 1. Serum or plasma alanine aminotransferase greater than 3 times the upper limit of normal
• 2. Serum or plasma total bilirubin greater than 2.5 times the upper limit of normal
• 3. Serum creatinine \> 2 times the upper limit of normal
• 4. Platelet count \< 75,000 cells/mm3
• 5. Absolute neutrophil count \<1,000 cells/mm3
• 6. Serum or plasma potassium \<3.5 meq/L (note: potassium may be repleted and test repeated)
• 17. Weight less than 40.0 kg
• 18. Known or suspected resistance to isoniazid or rifamycins (by phenotypic or molecular test)
• 19. Previously enrolled in this study or currently enrolled in another therapeutic clinical trial that, in the investigator's judgment, would compromise study integrity or participant safety
• 20. Current or planned incarceration or other involuntary detention.