MALABSORPTION OF ANTITUBERCULOUS DRUGS IN BOTSWANA

博茨瓦纳抗结核药物吸收不良

• 批准号: 2736209
• 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/2736209
• 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 估计全球结核病流行将导致90 本十年新增病例100万例，发病率最高的是 在撒哈拉以南非洲，艾滋病毒感染率也很高。 这 艾滋病毒和结核病之间日益增长的相互作用引起了人们的关注 关于常规抗结核治疗对艾滋病毒/结核病的疗效 患者 获得性结核病相关死亡率较高 据报道，感染艾滋病毒的结核病患者出现耐药性和复发。 一 这些不良结果的可能解释是生物利用度低 艾滋病患者的口服药物。 初步证据显示 HIV感染者抗结核药物的吸收不可靠 超过30%的HIV感染者可能会吸收不良， 他们的毒品 该提案概述了对540例结核病患者进行的为期3年的前瞻性队列研究 在博茨瓦纳哈博罗内的公主码头医院接受治疗。 基线， 临床、微生物学和实验室数据，包括HIV血清学和 异烟肼（H）、利福平（R）、乙胺丁醇（E）和吡嗪酰胺（P）血清 将获得浓度。 患者将接受18个月的随访 治疗结束后，评估结果。 横断面调查 将对入选的前100名患者进行测量， 药物吸收不良的患病率，并确定风险因素和可能的 吸收不良的机制。 在治疗期间死于结核病的患者， 获得耐药性或治疗后复发， 将确定发病率。 死于结核病或结核病复发的患者将 作为不同巢式病例对照研究的病例患者，以确定 吸收不良的治疗意义