Three Months of Weekly Rifapentine and Isoniazid for M. Tuberculosis Infection

INCLUSION criteria:

• Males or nonpregnant, non-nursing females > 2 years old.

• Tuberculin (PPD) skin test reactors at high risk for developing TB but withoutevidence of active TB. High-risk reactors are defined as:

1. Household and other close contacts of persons with culture-confirmed TB who areTST-positive as part of a contact investigation conducted within two years ofthe date of enrollment. Close contact is defined as > 4 hours in a sharedairspace during a one-week period. Among close contacts, a positive TST isdefined as > 5 mm induration after 5 TU of PPD placed intradermally using theMantoux technique.

2. TST converters--converting from a documented negative to positive TST within atwo-year period. This is defined as persons with a tuberculin skin test of > 10mm within two years of a nonreactive test or persons with an increase of > 10mm within a two-year period.

3. HIV-seropositive, TST positive (> 5 mm induration) persons.

4. Persons with > 2 cm2 of pulmonary parenchymal fibrosis on chest X-ray, no priorhistory of TB treatment, > 5 mm induration on TST, and 3 sputum culturesnegative for M. tuberculosis on final report.

• HIV-seropositive close contacts of persons with culture-confirmed TB, regardless ofTST status. In addition, HIV-seropositive close contacts of persons withculture-confirmed TB who have a documented history of completing an adequate courseof treatment for active TB or latent TB infection, are also eligible.

• Willing to provide signed informed consent, or parental consent and participantassent.

EXCLUSION criteria:

• Current confirmed culture-positive or clinical TB

• Suspected TB (as defined by the site investigator)

• Tuberculosis resistant to isoniazid or rifampin in the source case

• A history of treatment for > 14 consecutive days with a rifamycin or > 30consecutive days with INH during the previous 2 years.

• A documented history of a completing an adequate course of treatment for active TBor latent TB infection in a person who is HIV-seronegative.

• History of sensitivity/intolerance to isoniazid or rifamycins

• Serum aminotransferase aspartate (AST, SGOT) > 5x upper limit of normal amongpersons in whom AST is determined

• Pregnant or nursing females

• Persons currently receiving or planning to receive HIV-1 protease inhibitors ornonnucleoside reverse transcriptase inhibitors in the first 90 days afterenrollment.

• Weight < 10.0 kg