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To evaluate and compare the effectiveness of a 2-month regimen of rifampin and pyrazinamide versus a 1-year course of isoniazid (INH) to prevent the development of tuberculosis in patients who are coinfected with HIV and latent Mycobacterium tuberculosis (MTb). Current guidelines recommend 6 to 12 months of treatment with INH for purified protein derivative (PPD)-positive individuals. Problems with this treatment include compliance, adverse reaction, and the possibility of not preventing disease due to INH-resistant organisms. Studies suggest that two or three months of rifampin and pyrazinamide may be more effective than longer courses of INH. A two-month prevention course should help to increase compliance. In addition, the use of two drugs (rifampin and pyrazinamide) may help overcome problems with drug resistance. Current guidelines recommend 6 to 12 months of treatment with INH for purified protein derivative (PPD)-positive individuals. Problems with this treatment include compliance, adverse reaction, and the possibility of not preventing disease due to INH-resistant organisms. Studies suggest that two or three months of rifampin and pyrazinamide may be more effective than longer courses of INH. A two-month prevention course should help to increase compliance. In addition, the use of two drugs (rifampin and pyrazinamide) may help overcome problems with drug resistance. After baseline screening, patients are randomized to one of two treatment arms and are evaluated by means of clinic visits monthly for the first three months, then every three months for the first year (there are additional clinic visits for INH patients). Patients are then evaluated every six months. One group of patients takes INH plus vitamin B6 for 12 months. The other group of patients takes 1 of 2 doses of rifampin (depending on patient's weight) plus pyrazinamide in 3-4 divided doses for 60 days.
Inclusion Criteria Concurrent Medication: Allowed: * Antiretroviral treatment. * Pneumocystis carinii pneumonia prophylaxis. * Treatment for acute opportunistic infection/malignancy. * Aminoglycosides, quinolones or fluoroquinolones such as ciprofloxacin or ofloxacin for \< 14 days for treatment of intercurrent infection. Patients must have: * HIV infection. * Signed informed consent. * Reasonably good health at time of study entry. * Perceived life expectancy of at least six months. * Allowed: * Participation in other clinical trials as long as there is no potential activity of other study drugs against Mycobacterium tuberculosis (MTb), additive toxicities between study agents, or known possible drug interactions between study drugs. Prior Medication: Allowed: * Treatment with quinolones, fluoroquinolones, aminoglycosides, or other agents with known or potential activity against M. tuberculosis. Exclusion Criteria Co-existing Condition: Patients with the following conditions or symptoms are excluded: * Current active tuberculosis (confirmed or suspected). * Sensitivity or intolerance to study medication. * Acute hepatitis. * Evidence of peripheral neuropathy, i.e., signs or symptoms of paresis, paresthesias, neuromotor abnormalities, or neurosensory deficits of grade 3 or worse. * Inability to have concomitant medications changed to avoid serious interaction with study drug. Concurrent Medication: Excluded: - Quinolones, fluoroquinolones, or aminoglycosides with antituberculous activity (may be used for up to 14 days for treatment of intercurrent infection).Other agents with known or potential antituberculous activity should be avoided, including the following: * Aminosalicylic acid salts, capreomycin, clofazimine, cycloserine, ethambutol, ethionamide, isoniazid, kanamycin, pyrazinamide, rifabutin, rifampin, streptomycin, and thiacetazone. Prior Medication: Excluded: * History of treatment for \> 2 months with agents that have known or potential antituberculous activity other than those specifically allowed. Agents with potential or known antituberculous activity include the following: * Aminoglycosides such as amikacin, aminosalicylic acid salts, capreomycin, ciprofloxacin, clofazimine, cycloserine, ethambutol, ethionamide, isoniazid, kanamycin, ofloxacin, pyrazinamide, quinolones or fluoroquinolones, rifabutin, rifampin, streptomycin, and thiacetazone. Patients may not have: * Current active tuberculosis. * Acute hepatitis. * Peripheral neuropathy of grade 3 or grade 4. Willing and able, in the clinician's opinion, to comply with the treatment and clinical management issues.