RIFAPENTINE FOR RELAPSE AMONG HIV SEROPOSITIVE & SELECTED SERONEGATIVE

自1995年以来，杜克大学医学中心和达勒姆VAMC一直在参与CDC申办的一项多中心、3期利福霉素衍生物利福喷丁治疗肺支原体的疗效和安全性试验。在治疗的继续阶段中的结核病（IRB编号1861-97- 12 R3）。美国CDC利福喷丁临床试验的这一多中心子研究的目的是评估四个患者组中的药物药代动力学和复发的风险因素：1.艾滋病毒阳性患者，2。结核病治疗失败或复发者，3. HIV阴性对照，与每个HIV阴性失败或复发相匹配，以及4.利福喷丁临床试验中研究阶段治疗的所有HIV阴性参与者（称为“前瞻性组”）。具体目标是：1。研究异烟肼和利福霉素的药代动力学。为了确定INH乙酰化剂状态，3.测定异烟肼、利福平和利福喷丁的生物利用度。比较尿液和血液用于药代动力学筛选的情况。研究方法：在研究开始时，只包括利福喷丁临床试验的前两组;后来的修正案增加了其他两组。潜在的候选人包括3名HIV阳性患者，1名失败，1名复发，以及接受研究阶段治疗的患者。该研究正在一般临床研究中心（GCRC）进行，以门诊和住院患者为基础。在获得知情同意后，如果研究前肝功能检查结果在入组参数范围内，则每例患者接受单剂量INH和利福平或利福喷丁（无论他们在利福喷丁临床试验的研究阶段接受了哪种药物）。使用蛋白酶抑制剂的患者不接受利福霉素。对于目前在利福喷丁临床试验中接受治疗的患者，在药物剂量之前抽取血液。在给药后1、2、5和24小时抽血。接受利福喷丁的患者也在给药后48小时抽血。还抽取血液用于INH乙酰化状态、CBC、化学，并且对于HIV阳性者，用于CD 4计数和HIV病毒载量。在给药后5小时和24小时收集尿液。审查病历，并就合并用药、胃肠道症状和膳食对患者进行访谈。要求患者尽可能多地重复他们在研究阶段治疗期间服用的膳食和药物。如果他们正在服用新的药物，我们将与他们的医生讨论是否可以暂时停用药物。进展报告：迄今为止已入组4例患者。两个是艾滋病毒阳性（一个蛋白酶抑制剂），两个是前瞻性的患者。3例患者为非裔美国男性，1例为非裔美国女性。所有患者均耐受研究程序，无不良事件。如果有新的失败、复发或符合条件的前瞻性患者，明年可能会有患者入组。意义：这项研究解决了一个重要的公共卫生风险-艾滋病毒感染者的结核病。

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.