RIFAPENTINE FOR RELAPSE AMONG HIV SEROPOSITIVE & SELECTED SERONEGATIVE

美国疾病控制与预防中心利福喷丁临床试验(USPHS研究22)的这项多中心子研究的目的是在四组患者中评估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.艾滋病毒阴性对照，与每一次艾滋病毒阴性失败或复发相匹配，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)。在研究22中，36名接受利福喷丁治疗的HIV阳性患者中，有4人出现了耐利福平结核病复发，这项药代动力学亚研究是在此之后启动的。这项研究在综合临床研究中心(GCRC)进行。在获得知情同意后，每个患者接受单剂量的异烟肼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)。服用蛋白酶抑制剂的患者没有接受任何一种利福霉素。对于目前正在接受利福喷丁临床试验治疗的患者，在药物剂量之前抽血。分别于给药后1、2、5、24小时抽血。接受利福喷丁治疗的患者也在服药后48小时抽血。同时抽血检测异烟肼乙酰化状态、血细胞计数、化学成分，以及HIV阳性者的CD4计数和HIV病毒载量。分别于给药后5小时和24小时采集尿液。用于乙酰化状态、药代动力学和病毒载量的血浆被冷冻并运往中心实验室进行检测。复查了病历，并就伴随用药、胃肠道症状和进餐问题对患者进行了访谈。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。数据管理和分析将由疾控中心完成。对HIV阳性患者的初步分析将根据异烟肼乙酰化状态比较复发率和利福平耐药复发率。单变量分析将考虑每个受试者的药代动力学特征。

The purpose of this multi-center sub-study of the U.S. CDC Rifapentine Clinical Trial (USPHS Study 22) was 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). This pharmacokinetic sub-study was initiated following rifampin-resistant TB relapse which occurred in 4 of the 36 HIV-positive patients who received rifapentine in Study 22. The study was done on the General Clinical Research Center (GCRC). After informed consent was obtained, each patient received 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 did not receive either rifamycin. For patients who were currently receiving therapy in the Rifapentine Clinical Trial, blood was drawn just prior to the medication dose. Blood was drawn at 1, 2, 5, and 24 hours post dose. Patients who received rifapentine also had blood drawn at 48 hours post dose. Blood was also drawn for INH acetylator status, CBC, chemistries, and for those HIV-positive, for CD4 count and HIV viral load. Urine was collected at 5 and 24 hours post dose. Plasma for acetylator status, pharmacokinetics, and viral load was frozen and shipped to a central lab for testing. The medical record was reviewed and patients interviewed regarding concomitant medications, gastrointestinal symptoms, and meals. Patients were asked to duplicate, as much as possible, the meals and medications they took during study-phase therapy. Data management and analysis will be done by CDC. A primary analysis among HIV-positive patients will compare rates of relapse and of rifampin-resistant relapse by INH acetylator status. Univariate analyses will consider pharmacokinetic characteristics of each subject.