• Pulmonary TB (among individuals either without history of prior TB treatment or with history of TB treatment more than 5 years prior to study entry), identified within 7 days prior to study entry by at least one sputum specimen positive for Mtb by Xpert. Semiquantitative Mtb results of medium or high are required.

• Pulmonary TB with documented INH susceptibility (by Line Probe Assay (LPA) or Xpert MTB/XDR or other validated molecular test) and with documented RIF susceptibility (by LPA or Xpert MTB/RIF or Xpert MTB/RIF Ultra or other validated molecular test) within 7 days prior to study entry.

• Documentation of HIV-1 infection status, as below:

‣ Presence or Absence of HIV-1 infection, as documented by:

• Any licensed rapid HIV test or HIV-1 enzyme or chemiluminescence immunoassay (E/CIA) test kit, any time prior to study entry. AND

⁃ Confirmed by one of the following:

• A second antibody test from different manufacturers or based on different principles and epitopes (combination antigen-antibody-based rapid tests may be used), or

∙ HIV-1 antigen, or

∙ Plasma HIV-1 RNA viral load, or

∙ A licensed Western blot

• For individuals with HIV: CD4+ cell count ≥100 cells/mm3 based on testing performed within 30 days prior to study entry.

• For individuals with HIV: Currently being treated with dolutegravir-based antiretroviral therapy (ART), or plan to initiate dolutegravir-based ART at or before study week 8.

• Individuals age ≥18 years.

• The following laboratory values obtained within 7 days prior to study entry at any network-approved non-US laboratory that operates in accordance with Good Clinical Laboratory Practices (GCLP) and participates in appropriate external quality assurance programs:

‣ Serum or plasma alanine aminotransferase (ALT) ≤3 times the upper limit of normal (ULN)

⁃ Serum or plasma total bilirubin ≤2 times ULN

⁃ Serum or plasma creatinine ≤2 times ULN

⁃ Serum or plasma potassium ≥3.5 mEq/L

⁃ Serum or plasma magnesium ≥1.0 mEq/L (≥0.500 mmol/L)

⁃ Absolute neutrophil count (ANC) ≥1500/mm\^3

⁃ Hemoglobin ≥9.5 g/dL for individuals assigned to female sex at birth and ≥10.0 g/dL for individuals assigned to male sex at birth

⁃ Platelet count ≥100,000/mm\^3

⁃ Negative for hepatitis B core antibody (HBcAb) total, hepatitis B surface antigen (HBsAg)

⁃ Negative for hepatitis C virus (HCV) antibody (or if HCV antibody positive, must have a negative HCV PCR)

• For individuals assigned to female sex at birth and who are of reproductive potential, negative pregnancy test (urine HCG or serum β-HCG) within 3 days (72 hours) prior to entry by any network-approved non-US laboratory or clinic that operates in accordance with GCLP and participates in appropriate external quality assurance programs.

• Individuals assigned to female sex at birth, who are of reproductive potential, and who participate in sexual activity that could lead to pregnancy must agree to use at least two of the following forms of birth control while receiving TB study medications and for 12 months after stopping study medications:

⁃ Male or female condoms

⁃ Diaphragm or cervical cap (with spermicide, if available)

⁃ Intrauterine device (IUD) or intrauterine system (IUS)

⁃ Hormone-based birth control (e.g., oral contraceptives, Depo-Provera, NuvaRing, implants)

• For individuals who are assigned male sex at birth who engage in sexual activity that may lead to pregnancy in their partner must agree to either remain abstinent or use male contraceptives. They are also strongly advised to inform their non-pregnant sexual partners of reproductive potential to use effective contraceptives while the individual is on study and for 90 days after experimental treatment discontinuation.

⁃ For individuals assigned male sex at birth with pregnant partners, willingness to use condoms during vaginal intercourse while on study and for 90 days after experimental treatment discontinuation.

⁃ For individuals assigned male sex at birth, willingness to refrain from sperm donation while on study and for 90 days after experimental treatment discontinuation.

⁃ Documentation of Karnofsky performance score ≥60 obtained within 14 days prior to study entry.

⁃ Chest x-ray obtained within 14 days prior to study entry.

⁃ A verifiable address or residence readily accessible for visiting, and willingness to inform the study team of any change of address during study treatment and follow-up period.

⁃ Ability and willingness of individual to provide informed consent.