Assessment of the Safety, Tolerability, and Effectiveness of Rifapentine Given Daily for LTBI

Inclusion Criteria 1. Persons with LTBI who do not have evidence of TB disease (see exclusion criteria) and are at increased risk of progression to TB. LTBI or M. tuberculosis infection may be demonstrated by either a positive tuberculin skin test (TST) or a positive interferon gamma release assay (IGRA; e.g., QuantiFERON or T.SPOT.TB). Details of testing definitions and requirements for each risk factor are further described in the MOOP. Persons with LTBI at increased risk of progression to TB are those with at least one of the following: 1. Household and other close contacts (\> 4 hours of exposure in a one-week period) within 2 years prior to enrollment, of persons with bacteriologically confirmed TB. o Acceptable testing approaches for bacteriologic confirmation are 1) culture with rifamycin DST; or, 2) nucleic acid amplification tests (NAATs) that detect M. tuberculosis and detect mutations associated with rifamycin resistance. Additional details on bacteriologic confirmation, including accepted NAATs, will be included in the MOOP. 2. Recent M. tuberculosis infection, defined as converting from a documented negative to positive TST or IGRA within 2 years prior to enrollment. Persons without known close contact to someone with active pulmonary TB who have a conversion by IGRA may require additional evaluation to rule out a false conversion. Additional guidance and definitions of conversion are in the MOOP. 3. HIV co-infection (with CD4+ T-lymphocyte count \> 100 cells/mm3) 4. ≥ 2 cm2 of pulmonary parenchymal fibrosis on chest X-ray and no prior history of treatment for TB or LTBI. 5. Recent (within 3 years prior to enrollment) immigration to the United States or other country with low to moderate TB incidence, with abnormal chest X-ray, and no evidence of active TB. 6. Recent (within 3 years prior to enrollment) immigration to the United States or other country with low to moderate TB incidence, from a country with an estimated incidence rate of TB \> 150 per 100,000 (see Appendix D) and either a positive IGRA or a TST ≥15 mm (TST \> 15 mm only applicable for those with recent immigration as their only risk factor for progression to TB). 7. Recent (within 3 years prior to enrollment) immigration and seeking refugee/asylum status (see MOOP for additional details) to the United States or other country with low to moderate incidence from a country with an estimated incidence rate of TB \> 75 per 100,000 (see Appendix E) and either a positive IGRA or a TST ≥15 mm (TST \> 15 mm only applicable for those with recent immigration as their only risk factor for progression to TB). 8. Individuals with an increased risk of TB due to medical conditions such as end-stage renal disease. 9. Individuals currently using immunosuppressive medications such as chronic steroids. 10. Individuals with planned use of TNF-α inhibitors. 11. Individuals with planned solid organ or hematologic transplantation 2. Willing to provide signed informed consent, or parental permission and participant assent. 3. For the following special populations, both inclusion criteria above must be met AND the criteria below depending on stage: 1. Pregnant women in their second or third trimester (≥14 weeks gestation). * Stage 1: Include only those who agree to participate in the semi-intensive PK component. * Stage 2: Include regardless of semi-intensive PK component participation. 2. Children aged less than 12 years * Stage 1: Include only those who agree to participate in the semi-intensive PK component, based on enrollment strategy presented in Appendix I. * Stage 2: Include regardless of semi-intensive PK component participation, based on PK findings and enrollment strategy described in Appendix I. Exclusion Criteria 1. Failure to document positive IGRA or TST 2. Current breastfeeding. 3. Women who are currently pregnant in their first trimester (\<14 weeks gestation) or intend to become pregnant within 120 days of enrollment. 4. Non-pregnant women of childbearing potential who refuse to practice an adequate method of contraception (barrier method or non-hormonal intrauterine device) or abstain from activities that could lead to pregnancy. 5. Current culture-positive TB, clinical TB, or suspected current TB. (Includes cases in which active TB cannot be excluded with reasonable clinical certainty by the site investigator. If sputum samples have been collected AND site investigators have suspicion of active TB, site investigators must wait to review culture results prior to enrollment.) 6. TB resistant to any rifamycin in the source case 7. A history of treatment for \> 7 consecutive days (if daily dosing) with a rifamycin or \>1 week (if weekly dosing) with a rifamycin and INH or \> 30 consecutive days with INH within 2 years prior to enrollment. 8. A documented history of completing an adequate course of treatment for TB disease or LTBI in a person who is HIV-seronegative. 9. History of allergy or intolerance to rifamycins. 10. Serum alanine aminotransferase (ALT; SGPT) or serum aspartate aminotransferase (AST; SGOT) \> 5x upper limit of normal among persons in whom screening ALT or AST is determined. 11. Receiving concomitant medications that are known to be contraindicated with any study drug. 12. Weight \< 25 kg for participants ≥ 12 years, and weight \< 3kg for participants \< 12 years