Inclusion Criteria:
* Informed consent obtained and signed.
* Male or female, aged ≥18 years.
* Pulmonary TB diagnosed by Xpert MTB/RIF, Xpert MTB/RIF Ultra, Line Probe Assay (LPA), or mycobacterial culture.
* Sputum positive for acid fast bacilli (at least 1+ grade on the WHO scale).
* Pulmonary TB diagnosed without known INH resistance (by LPA or Xpert MTB/XDR) and without known RIF resistance (by either LPA or Xpert). Note that phenotypic DST for INH resistance will be done on screening cultures (using MGIT). If baseline molecular or phenotypic test results that become available after enrollment detect resistance to INH or RIF, the participant will be a late exclusion from the study.
* Newly diagnosed with TB and have a history of being untreated for at least 6 months after cure from a previous episode of TB.
* For participants living with HIV, CD4+ cell count ≥200 cells/mm3, obtained within 30 days prior to study entry. Enrollment of participants living with HIV will be limited to no more than 20% of the total study population.
* For participants living with HIV, must be currently receiving or planning to initiate ART at or before study week 8.
* Laboratory values at study screening:
* Alanine aminotransferase (ALT) ≤3x the upper limit of normal (ULN)
* Total bilirubin ≤2.5 x ULN
* Creatinine ≤2 x ULN
* Potassium ≥3.5 mEq/L, ≤5.5 mEq/L
* Absolute neutrophil count (ANC) ≥650/mm3
* Hemoglobin ≥7.0g/dL
* Platelet count ≥50,000/mm3
* For females of reproductive potential, negative serum or urine pregnancy test within 5 days prior to entry and willingness to use effective contraception for the duration of the study. Female participants who are not of reproductive potential must have documentation of menopause, hysterectomy, or bilateral oophorectomy or bilateral tubal ligation. Acceptable forms of contraception include: condoms, intrauterine device or intrauterine system, cervical cap with spermicide, diaphragm with spermicide.
* The initial 25% of enrollment will be restricted to participants (n = 39) with mild or moderate disease, defined as having sputum with higher Xpert MTB/RIF cycle threshold (Ct) values (\> 17 cycles) and the absence of extensive lung disease on chest X-ray (involvement of at least half of the area of the entire thoracic cavity). Thereafter, all eligible patients will be offered participation without a pause in enrollment.
Exclusion Criteria:
* More than 5 days of treatment directed against active TB for the current TB episode preceding study entry.
* Current extrapulmonary TB (e.g. neurological, skeletal, abdominal, or nodal), not including pleural TB, in the opinion of the site investigator.
* Pregnant or breastfeeding.
* Weight \<30kg.
* Inability to take oral medications.
* Current or planned use of any drug known to severely prolong the QTc interval, including, but not limited to: amiodarone, amitriptyline, chloroquine, chlorpromazine, cisapride, disopyramide, erthyromycin, moxifloxacin, procainamide, quinidine, or sotalol.
* Current or planned use of one or more of the following HIV medications: HIV protease inhibitors, HIV non-nucleoside reverse transcriptase inhibitors, elvitegravir/cobicistat, or bictegravir.
* Current or past use of clofazimine, bedaquiline or delamanid.
* QTcF \>450ms for men or \>470 ms for women.
* Current or history of known personal or family long QT syndrome.
* Known allergy/sensitivity to components of study TB drugs or their formulation.
Microbiologic confirmation of drug-susceptible TB is not always available at the time of enrollment. Enrolled individuals who are subsequently determined to meet either of the following criteria will be classified as late exclusions and study treatment will be discontinued. These participants will be transitioned to routine care but requested to remain in study follow up for safety evaluations.
A. Screening, baseline study, and Week 1 visit sputum cultures fail to grow M. tuberculosis.
B. Resistance to RIF or INH is detected from baseline molecular or phenotypic testing results that become available after enrollment.
