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一直在参与一项由疾病预防控制中心赞助的、多中心的新型利福霉素衍生物利福喷丁的3期疗效和安全性试验，用于治疗处于继续治疗阶段的肺结核(IRB编号1861-97-12R3)。美国疾病控制与预防中心利福喷丁临床试验的这项多中心子研究的目的是评估四组患者的药物药代动力学和复发风险因素：1.艾滋病毒阳性患者，2.未接受结核病治疗或复发的患者，3.与艾滋病毒阴性的失败或复发相匹配的艾滋病毒阴性对照，以及4.在利福喷丁临床试验中接受研究阶段治疗的所有艾滋病毒阴性参与者(称为“预期组”)。具体目标是：1.研究异烟肼和利福霉素的药代动力学；2.确定异烟肼的乙酰化状态；3.测定异烟肼、利福平和利福喷丁的生物利用度；4.比较尿液和血液在药代动力学筛选中的作用。方法：在研究开始时，只包括利福喷丁临床试验的前两组；后来的修订增加了另外两组。潜在的候选对象包括3名艾滋病毒阳性患者，1名失败，1名复发，以及接受研究阶段治疗的患者。这项研究是在综合临床研究中心(GCRC)进行的，分为门诊和住院两个阶段。在获得知情同意后，如果研究前肝功能测试在登记参数范围内，每个患者将接受单剂量异烟肼和利福平或利福喷丁(无论是他们在利福喷丁临床试验的研究阶段获得的)。服用蛋白酶抑制剂的患者不会接受这两种药物中的任何一种。对于目前正在接受利福喷丁临床试验治疗的患者，在药物剂量之前抽血。在服药后1、2、5和24小时抽血。接受利福喷丁治疗的患者也会在服药后48小时抽血。此外，还会抽血检测异烟肼乙酰化状态、血细胞、化学成分，以及HIV阳性者的CD4计数和HIV病毒载量。在服药后5小时和24小时收集尿液。审查医疗记录，并就伴随药物、胃肠道症状和进餐问题与患者进行面谈。患者被要求尽可能多地复制他们在研究阶段治疗期间所吃的食物和药物。如果他们正在服用新药，我们将与他们的医生讨论是否可以暂时停止服药。进展报告：到目前为止已有4名患者入选。两名HIV阳性患者(一名服用蛋白酶抑制剂)和两名潜在患者。三名患者是非洲裔美国男性，一名非裔美国女性。所有人都能忍受研究过程，没有不良反应。如果有新的失败、复发或符合条件的潜在患者，可能会有患者在下一年登记。意义：这项研究解决了一种重要的公共卫生风险--艾滋病毒感染者中的结核病。

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.