MALABSORPTION OF ANTITUBERCULOUS DRUGS IN BOTSWANA

博茨瓦纳抗结核药物吸收不良

• 批准号: 6031048
• 负责人: Philip C Hopewell
• 金额: $ 2.32万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-30 至 2000-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6031048
• 关键词: Africa; HIV infections; antitubercular agents; clinical research; drug resistance; drug screening /evaluation; ethambutol; gastrointestinal drug absorption; human subject; human therapy evaluation; isoniazid; longitudinal human study; malabsorption; microorganism disease chemotherapy; oral administration; outcomes research; pharmacokinetics; pyrazinamide; relapse /recurrence; rifamycins; tuberculosis

DESCRIPTION Estimates suggest the global tuberculosis [TB] epidemic will result in 90 million new cases this decade, with the highest incidence rates occurring in sub-Saharan Africa where the prevalence of HIV infection is also high. This growing interface between the HIV and TB epidemics has raised concerns regarding the efficacy of conventional antituberculosis therapy in HIV/TB patients. Higher rates of TB-associated mortality, acquired drug-resistance, and relapse have been reported in TB patients with HIV. A potential explanation for these adverse outcomes is the low bioavailability of oral medications in HIV patients. Preliminary evidence suggests the oral absorption of anti-tuberculosis drugs is unreliable in HIV-infected patients, and that more than 30 % of all HIV-infected patients may malabsorb their drugs. This proposal outlines a 3 year prospective cohort study of 540 TB patients admitted to the Princess Marina Hospital in Gaborone, Botswana. Baseline, clinical, microbiologic, and laboratory data, including HIV serologies and serum for isoniazid (H), rifampin (R), ethambutol (E), and pyrazinamide (P) concentrations will be obtained. Patients will be followed for 18 months after the completion of therapy to assess outcome. A cross-sectional survey of the first 100 patients enrolled will be performed to measure the prevalence of drug malabsorption, and to identify risk factors and possible mechanisms for malabsorption. Patients who die of TB while on therapy, acquire drug-resistance, or relapse following therapy will be identified and incidence rates will be determined. Patients who die of TB or relapse will serve as case patients in different nested case-control studies to determine the therapeutic significance of malabsorption.

描述 估计表明全球结核病[TB]流行将导致90 这个十年的百万个新病例，发病率最高 撒哈拉以南非洲的患病率也很高。 这 艾滋病毒和结核病流行病之间不断增长的界面引起了人们的关注 关于常规抗结核疗法在HIV/TB中的功效 患者。 获得结核病相关的死亡率较高，获得 艾滋病毒的结核病患者已经报道了药物抗药性和复发。 一个 这些不良结果的潜在解释是低生物利用度 艾滋病毒患者的口服药物。 初步证据表明口头 抗结核药物的吸收在HIV感染中是不可靠的 患者，所有感染HIV的患者中有超过30％可能会出现 他们的毒品。 该提案概述了540名TB患者的3年前瞻性队列研究 被博茨瓦纳Gaborone的玛丽娜公主医院入院。 基线， 临床，微生物和实验室数据，包括HIV血清学和 Isoniazid（H），Rifampin（R），Ethambutol（E）和​​吡嗪酰胺（P）的血清 将获得浓度。 患者将持续18个月 完成治疗后，以评估结果。 横断面调查 在入学的前100名患者中，将进行测量 药物吸收不良的患病率，并确定危险因素和可能 吸收不良的机制。 治疗期间死于结核病的患者， 将确定获得药物抗药性或治疗后复发，并 将确定发病率。 死于结核病或复发的患者将 在不同的嵌套病例对照研究中充当病例患者，以确定 吸收不良的治疗意义。