Since 1995, Duke University Medical Center and the Durham VAMC have been participating in a CDC-sponsored, multi-center, Phase 3 efficacy and safety trial of a new rifamycin derivative, rifapentine, for the treatment of pulmonary M. tuberculosis in the continuation phase of therapy (IRB Number 1861-97-12R3). The purpose of this multi-center sub-study of the U.S. CDC Rifapentine Clinical Trial is to evaluate drug pharmacokinetics and risk factors for relapse among four patient groups: 1. HIV-positive patients, 2. those who failed TB treatment or relapsed, 3. HIV-negative controls, matched to each HIV-negative failure or relapse, and 4. all HIV-negative participants on study-phase therapy in the Rifapentine Clinical Trial (referred to as the """"""""prospective group""""""""). Specific objectives are: 1. To study INH and rifamycin pharmacokinetics, 2. To define INH acetylator status, 3. To determine the bioavailability of INH, rifampin, and rifapentine, and 4. To compare the use of urine and blood for pharmacokinetic screening. Methods: At the beginning of the study, only the first two groups from the Rifapentine Clinical Trial were included; a later amendment added the other two groups. Potential candidates have included 3 HIV-positive patients, one failure, one relapse, and those receiving study-phase therapy. The study is being done on the General Clinical Research Center (GCRC), on an outpatient and inpatient basis. After informed consent has been obtained and if pre-study liver function tests are within the enrollment parameters, each patient receives a single dose of INH and either rifampin or rifapentine (whichever they received in the study phase of the Rifapentine Clinical Trial). Patients on protease inhibitors do not receive either rifamycin. For patients currently receiving therapy in the Rifapentine Clinical Trial, blood is drawn just prior to the medication dose. Blood is drawn at 1, 2, 5, and 24 hours post dose. Patients who receive rifapentine also have blood drawn at 48 hours post dose. Blood is also drawn for INH acetylator status, CBC, chemistries, and for those HIV-positive, for CD4 count and HIV viral load. Urine is collected at 5 and 24 hours post dose. The medical record is reviewed and patients interviewed regarding concomitant medications, gastrointestinal symptoms, and meals. Patients are asked to duplicate, as much as possible, the meals and medications they took during study-phase therapy. If they are taking new medications, we will discuss with their physician whether the medications can be temporarily discontinued. Progress Report: Four patients have been enrolled to date. Two were HIV-positive (one on a protease inhibitor) and two were prospective patients. Three patients were African-American males and one was an African-American female. All tolerated the study procedures without adverse events. There may be patients enrolled in the next year, if there are new failures, relapses, or eligible prospective patients. Significance: This study addresses an important public health risk - tuberculosis in HIV infected individuals.
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