RIFAPENTINE FOR RELAPSE AMONG HIV SEROPOSITIVE & SELECTED SERONEGATIVE

自1995年以来，杜克大学医学中心和Durham VAMC一直参与cdc赞助的一项多中心的三期疗效和安全性试验，该试验是一种新的利福霉素衍生物利福喷丁，用于治疗处于继续治疗阶段的肺结核分枝杆菌（IRB编号1861-97-12R3）。美国CDC利福喷丁临床试验多中心亚研究的目的是评估四组患者的药物药代动力学和复发危险因素：2名hiv阳性患者；结核病治疗失败或复发者；hiv阴性对照，与每个hiv阴性失败或复发相匹配；在利福喷丁临床试验中接受研究期治疗的所有hiv阴性参与者（称为“前瞻性组”）。具体目标有：研究INH与利福霉素的药代动力学；定义INH乙酰化状态，3。3 .测定INH、利福平和利福喷丁的生物利用度；比较尿液和血液在药代动力学筛选中的应用。方法：在研究开始时，仅纳入利福喷丁临床试验的前两组；后来的修正案增加了另外两组。潜在的候选人包括3名hiv阳性患者，1名失败患者，1名复发患者和接受研究阶段治疗的患者。该研究正在普通临床研究中心（GCRC）进行，以门诊和住院为基础。在获得知情同意后，如果研究前肝功能测试在入组参数范围内，每位患者接受单剂量INH和利福平或利福喷丁（在利福喷丁临床试验的研究阶段接受的任一剂量）。使用蛋白酶抑制剂的患者不使用利福霉素。对于目前正在接受利福喷丁临床试验治疗的患者，在给药之前抽血。在给药后1、2、5和24小时抽血。接受利福喷丁治疗的患者也在给药后48小时抽血。还抽血检测乙酰化酶状态、全血细胞计数、化学反应，对HIV阳性患者，抽血检测CD4计数和HIV病毒载量。在给药后5和24小时收集尿液。审查医疗记录，并就伴随用药、胃肠道症状和膳食对患者进行访谈。患者被要求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药。进展报告：迄今已有4名患者入组。其中两人是hiv阳性（一人服用蛋白酶抑制剂），另外两人是潜在患者。三名患者是非裔美国男性，一名是非裔美国女性。所有患者均能耐受研究过程，无不良事件发生。如果有新的失败、复发或符合条件的潜在患者，明年可能会有患者入组。意义：本研究解决了一个重要的公共卫生风险——HIV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.