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.

Condition	Treatment or Intervention
HIV Infections Tuberculosis	Drug: Isoniazid  Drug: Pyrazinamide  Drug: Pyridoxine hydrochloride  Drug: Rifampin

Further Study Details: 

Expected Total Enrollment:  2000

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.

Ages Eligible for Study:  13 Years and above,  Genders Eligible for Study:  Both

Criteria

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.

California
      Community Consortium / UCSF, San Francisco,  California,  94110,  United States
Colorado
      Denver CPCRA / Denver Public Hlth, Denver,  Colorado,  802044507,  United States
Connecticut
      Hill Health Corp, New Haven,  Connecticut,  06519,  United States
Delaware
      Wilmington Hosp / Med Ctr of Delaware, Wilmington,  Delaware,  19899,  United States
District of Columbia
      Veterans Administration Med Ctr / Regional AIDS Program, Washington,  District of Columbia,  20422,  United States
Georgia
      AIDS Research Consortium of Atlanta, Atlanta,  Georgia,  30308,  United States
Illinois
      AIDS Research Alliance - Chicago, Chicago,  Illinois,  60657,  United States
      Chicago Dept of Health / Speciality STD Clinic, Chicago,  Illinois,  60605,  United States
Louisiana
      Louisiana Comm AIDS Rsch Prog / Tulane Univ Med, New Orleans,  Louisiana,  70112,  United States
Maryland
      Johns Hopkins Univ / School of Hygiene & Public Health, Baltimore,  Maryland,  212052179,  United States
      Johns Hopkins Univ / Brazil, Baltimore,  Maryland,  21205,  United States
Massachusetts
      Boston Dept of Health and Hosps, Boston,  Massachusetts,  02118,  United States
Michigan
      Henry Ford Hosp, Detroit,  Michigan,  48202,  United States
      Comprehensive AIDS Alliance of Detroit, Detroit,  Michigan,  48201,  United States
New Jersey
      Lattimore Comprehensive Pulmonary Disease Clinic, Newark,  New Jersey,  07103,  United States
      Saint Michael's Med Ctr, Newark,  New Jersey,  07102,  United States
      North Jersey Community Research Initiative, Newark,  New Jersey,  071032842,  United States
      Southern New Jersey AIDS Cln Trials / Dept of Med, Camden,  New Jersey,  08103,  United States
New York
      Harlem AIDS Treatment Group / Harlem Hosp Ctr, New York,  New York,  10037,  United States
      Bronx Lebanon Hosp Ctr, Bronx,  New York,  10456,  United States
      Clinical Directors Network of Region II, New York,  New York,  10011,  United States
      Addiction Research and Treatment Corp, Brooklyn,  New York,  11201,  United States
      Beth Israel Med Ctr, New York,  New York,  10035,  United States
Pennsylvania
      Philadelphia FIGHT, Philadelphia,  Pennsylvania,  19107,  United States
Virginia
      Richmond AIDS Consortium, Richmond,  Virginia,  23298,  United States

Study chairs or principal investigators

Gordin F,  Study Chair
Brown LS,  Study Chair

Study ID Numbers:  CPCRA 004; TB/PPD+; ACTG 177
Record last reviewed:  August 2004
Last Updated:  April 7, 2005
Record first received:  November 2, 1999
ClinicalTrials.gov Identifier:  NCT00000636
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08