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

Inclusion Criteria: * Males or non-pregnant, non-breastfeeding females \> 12 years old. Women of child-bearing potential who are not surgically sterilized must agree to practice an adequate method of contraception (barrier method or non-hormonal intrauterine device) or abstain from heterosexual intercourse during study drug treatment. * Persons with LTBI who do not have evidence of TB disease and are at increased risk of progression to TB. 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). Persons with LTBI at increased risk of progression to TB are those with 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 culture-confirmed TB A positive nucleic acid amplification test (NAAT)/GeneXpert in the source case may be used for enrollment prior to culture confirmation 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. 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 2 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 7. An increased risk of TB due to medical conditions such as end-stage renal disease, or due to use of immunosuppressive medications such as chronic steroids or TNF-alpha inhibitors. * Willing to provide signed informed consent, or parental permission and participant assent. Exclusion Criteria: * Current confirmed culture-positive or clinical TB. * Suspected current TB. Includes cases in which active TB cannot be eliminated as a possibility (by the site investigator) * TB resistant to any rifamycin in the source case * A history of treatment for \> 7 consecutive days with a rifamycin or \> 30 consecutive days with INH within 2 years prior to enrollment. * A documented history of completing an adequate course of treatment for TB disease or LTBI in a person who is HIV-seronegative. * History of allergy or intolerance to rifamycins. * Serum alanine aminotransferase (ALT; SGPT) or serum aspartate aminotransferase (AST; SGOT) \> 5x upper limit of normal among persons in whom baseline ALT or AST is determined+. * HIV-seropositive and on antiretroviral therapy that cannot be given with rifampin or rifapentine due to drug-drug interactions. * Receiving concomitant medications that are known to be contraindicated with any study drug. * Females who are currently pregnant, breastfeeding, or intend to become pregnant within 120 days of enrollment. * Weight \< 25 kg.