High-Dose Isoniazid Among Adult Patients With Different Genetic Variants of INH-Resistant Tuberculosis (TB)

Inclusion Criteria for Step 1: * New or recurrent pulmonary TB with sputum positive for acid-fast bacilli on direct microscopy of at least grade 1+ (International Union Against Tuberculosis and Lung Disease \[IUATLD\] scale) at the study laboratory on at least one pre-treatment sputum sample within 14 days prior to entry. * Infected with an M. tuberculosis strain for which Hain GenoType MTBDRplus genotype, performed at the study laboratory within 14 days prior to study entry, reveals one of the following results for INH susceptibility testing: * inhA promoter or functional mutation only (Group 1 participants, eligible for Steps 1 and 2) * No mutations in the inhA or katG genes (Group 2 participants, eligible for Step 1 and, during Stage 2 of the study, also eligible for Step 2) * katG mutation with or without an inhA mutation (Group 3 participants, eligible for Step 1 and, during Stage 2 of the study, also eligible for Step 2) * Ability and willingness of the participant or legal guardian/representative to provide informed consent. Inclusion Criteria for Step 2: * Entry into Step 1. * During Stage 1 of the protocol: inhA promoter or functional mutation only (Group 1). * During Stage 2 of the protocol: inhA promoter or functional mutation only (Group 1) OR mutations in neither inhA nor katG genes (Group 2) or mutation in the katG gene, with or without mutations in inhA promoter or functional genes (Group 3). * Body weight: 40 kg to 90 kg, inclusive. * Laboratory values obtained within 30 days prior to entry: * Absolute neutrophil count (ANC) \>=750 cells/mm\^3 * Hemoglobin \>= 7.4 g/dL * Platelet count \>= 50,000/mm\^3 * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \<=3 X upper limit of normal (ULN) * Total bilirubin \<=2.5 X ULN * HIV infection status must be documented as either absent or present, as defined below: Absence of HIV-1 infection within 30 days prior to Step 2 entry OR HIV-1 infection at any time prior to Step 2 entry. * For HIV-positive candidates only: CD4+ cell count of \>=50 cells/mm\^3, performed within 7 days prior to entry at a DAIDS-approved laboratory * For females of reproductive potential, negative serum or urine pregnancy test within 7 days prior to entry. Female participants who are participating in sexual activity that could lead to pregnancy must agree to use one reliable non-hormonal method of contraception (condoms or an IUD), or another method (diaphragm or cervical cap) if it is approved by the national regulatory authority and used according to package insert, while receiving study medications. * Willingness to be hospitalized for a minimum of 9 consecutive days. * Ability to produce an overnight sputum sample of sufficient quality and quantity. Exclusion Criteria for Step 1: -There are no exclusion criteria for Step 1. Exclusion Criteria for Step 2: -Current treatment with INH or receipt of INH during the 7 days prior to Step 2 entry. NOTE: Participants who have been started on INH-containing anti-TB treatment and have received this treatment for less than or equal to 2 weeks, but for whom TB drugs have been discontinued because of resistance to INH (with or without resistance to RIF), can participate in the study, but may need to be hospitalized, at the discretion of the investigator, while these drugs wash out; the minimum washout period for these drugs is 7 days. * Protocol versions 1.0 and 2.0 only: Any prior history of treatment for MDR-TB with second-line anti-TB drugs. This includes all drugs with anti-TB activity, except INH, RIF, ethambutol, pyrazinamide, and streptomycin. * Protocol versions 1.0 and 2.0 only: Receipt of more than 7 cumulative days of antibiotics intended for bacterial treatment that may have anti-TB activity, including amoxicillin/clavulanate (Augmentin), linezolid, metronidazole, or drugs from the quinolone class, with any of those days falling within the 14 days prior to Step 1 screening sputum collection. * Protocol version 3.0 only: Receipt of more than 7 cumulative days of second-line anti-TB drugs (including all drugs with anti-TB activity, except INH, RIF, ethambutol, pyrazinamide, and streptomycin) and/or antibiotics intended for bacterial treatment that may have anti-TB activity, including amoxicillin/clavulanate (Augmentin), linezolid, metronidazole, or drugs from the quinolone class, with any of those days falling within the 14 days prior to Step 1 screening sputum collection. The minimum washout period for these drugs is 7 days prior to Step 2 pre-entry sputum collection. * Known exposure to a person diagnosed with extensively drug-resistant (XDR)-TB or known personal diagnosis of XDR-TB in the past. * Protocol version 1.0: For HIV+ participants only: Current treatment, or treatment within 30 days prior to entry, with antiretroviral therapy (ART) or expected to initiate ART within 8 days after Step 2 entry. Prior receipt of ART for the prevention of mother-to-child-transmission is not exclusionary. * Breastfeeding. * Known allergy/sensitivity to INH. * Karnofsky score \<60 or poor general condition where any delay in full TB treatment cannot be tolerated in the opinion of the investigator (at screening). * Any of the following co-morbidities, complications, or underlying medical conditions: * Known current neurological TB (eg, TB of the spine, TB meningitis) * Peripheral neuropathy \>=Grade 2 within 14 days prior to entry * Current or history of epilepsy, defined as seizure disorder requiring current treatment with an antiepileptic medicine or history of any seizures within the prior year * Any condition as determined by physical examination, medical history, laboratory data, or chest x-ray which, in the opinion of the investigator, would interfere with participation in the study.