The Treatment of Tuberculosis in HIV-Infected Patients

Study Overview
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Brief Summary
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PER 5/30/95 AMENDMENT: To compare the combined rate of failure during therapy and relapse after therapy between two durations of intermittent therapy (6 versus 9 months) for the treatment of pulmonary tuberculosis (TB) in HIV-infected patients. To compare toxicity, survival, and development of resistance in these two regimens. ORIGINAL: To compare the efficacy and safety of induction and continuation therapies for the treatment of pulmonary TB in HIV-infected patients who are either from areas with known high rates of resistance to one or more anti-TB drugs or from areas where TB is expected to be susceptible to commonly used anti-TB drugs. PER 5/30/95 AMENDMENT: In HIV-negative patients, intermittent anti-TB therapy has been shown to be as effective as daily therapy, but the optimal duration of therapy in HIV-infected patients has not been established. ORIGINAL: In some areas of the country, resistance to one or more of the drugs commonly used to treat TB has emerged. Thus, the need to test regimens containing a new drug exists. Furthermore, the optimal duration of anti-TB therapy for HIV-infected patients with TB needs to be determined.

Detailed Description
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PER 5/30/95 AMENDMENT: In HIV-negative patients, intermittent anti-TB therapy has been shown to be as effective as daily therapy, but the optimal duration of therapy in HIV-infected patients has not been established. ORIGINAL: In some areas of the country, resistance to one or more of the drugs commonly used to treat TB has emerged. Thus, the need to test regimens containing a new drug exists. Furthermore, the optimal duration of anti-TB therapy for HIV-infected patients with TB needs to be determined. PER 5/30/95 AMENDMENT: Patients who have received an acceptable induction regimen prior to study entry and have been found to be susceptible to isoniazid and rifampin with no pyrazinamide resistance are randomized to receive either isoniazid or rifampin plus vitamin B6 biweekly for 18 or 31 weeks. Patients are evaluated at months 1, 2, 4, 6, 8, and 10, and every 4 months thereafter. Minimum follow-up is 1.5 years. ORIGINAL: In the induction phase, patients enrolled in drug-susceptible areas (defined as metropolitan areas with a resistance rate for isoniazid therapy of less than 10 percent) receive four drugs: isoniazid (plus pyridoxine), rifampin, pyrazinamide, and ethambutol. Patients enrolled in drug-resistant areas (resistance rate for isoniazid of 10 percent or higher) receive the four-drug regimen with or without a fifth drug, levofloxacin. After 8 weeks of induction, patients with multi-drug resistance are removed from study regimens; all other patients enter a continuation phase. Pansusceptible patients (showing susceptibility to all first-line anti-TB drugs) receive two study drugs for an additional 18 or 31 weeks; patients with isoniazid-resistant (or intolerant) TB receive two or three study drugs for an additional 44 weeks, while those with rifampin-resistant TB receive two or three study drugs for an additional 70 weeks. Patients are evaluated every 2 weeks in the induction phase and every 12 weeks in the continuation phase. Minimum follow-up is 2 years.

Official Title
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The Treatment of Pulmonary Mycobacterium Tuberculosis in HIV Infection

Conditions
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HIV Infections, Tuberculosis

Intervention / Treatment
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* Drug: Ethambutol hydrochloride
* Drug: Isoniazid
* Drug: Pyrazinamide
* Drug: Pyridoxine hydrochloride
* Drug: Levofloxacin
* Drug: Rifampin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Patients must have: INDUCTION PHASE (ELIMINATED PER 5/30/95 AMENDMENT). HIV infection. Diagnosis of pulmonary TB. NOTE: Patients from susceptible areas may be 13 years of age or older. Patients from resistant areas must be 18 years of age or older. CONTINUATION PHASE. Successful completion of induction phase and confirmation of TB by culture and susceptibility results. Susceptibility to and tolerance of isoniazid and rifampin and no resistance to pyrazinamide. HIV infection. Exclusion Criteria Co-existing Condition: Patients with the following symptoms or conditions are excluded: Multi-drug resistance to at least isoniazid and rifampin or known to have had close contact with a person with known multi-drug resistant TB. Known treatment-limiting reaction to any of the study drugs. Other disorders or conditions for which the study drugs are contraindicated. Concurrent Medication: Excluded: Other medications with anti-TB activity.

Ages Eligible for Study
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Minimum Age: 13 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Ethambutol hydrochloride|nan|
|Drug: Isoniazid|nan|
|Drug: Pyrazinamide|nan|
|Drug: Pyridoxine hydrochloride|nan|
|Drug: Levofloxacin|nan|
|Drug: Rifampin|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Isoniazid, Tuberculosis, Pulmonary, Pyrazinamide, Pyridoxine, Ofloxacin, Rifampin, AIDS-Related Opportunistic Infections, Ethambutol, Acquired Immunodeficiency Syndrome