Novel TB Prevention Regimens for HIV-Infected Adults

针对艾滋病毒感染者的新型结核病预防方案

• 批准号: 6749585
• 负责人: Richard E. Chaisson
• 金额: $ 76.83万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-07 至 2006-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6749585
• 关键词: Africa; African; HIV infections; Mycobacterium tuberculosis; adult human (21+); antitubercular agents; chemoprevention; comorbidity; disease /disorder prevention /control; human subject; human therapy evaluation; isoniazid; patient oriented research; pyrazinamide; rifamycins; tuberculosis

DESCRIPTION: (provided by applicant) Tuberculosis (TB) continues to kill approximately 2 million people per year, and is a major cause of HLV-related morbidity and mortality in developing countries. In addition, TB appears to cause a more rapid progression of HIV disease even when it is successfully treated, as active TB causes upregulation of HIV replication through several mechanisms. Although the World Health Organization has promoted a strategy of treatment of active TB as the principal weapon for TB control, accumulating evidence indicates that preventive therapy is required, particularly in countries with a high HIV burden. Both isoniazid (INH) and rifampin and pyrazinamide (RIF/PZA) have been shown to be effective in reducing the short-term incidence of TB in HIV-infected, tuberculin positive people, but the long-term benefit is not clear. Moreover, the implementation of TB preventive therapy programs in developing countries has been hindered by multiple factors. Establishment of clinical infrastructures to provide preventive therapy, concerns about adherence to treatment regimens, and a high likelihood of reinfection with subsequent increased risk of primary TB have been suggested as reasons not to implement preventive programs for HIV-infected populations. The purpose of this trial is to determine the effectiveness of three novel treatments on the risk of TB in a population of HIV-infected adults receiving clinical care and follow up in Soweto, South Africa. We will randomize 1141 adults with HIV infection and a reactive tuberculin skin test to receive weekly rifapentine and INH (RPT/INH) for 12 weeks, twice-weekly rifampin and pyrazinamide (RIFIPZA) for 8 weeks, continuous INH daily indefinitely (INH-C), or the internationally accepted standard of INH daily for six months (INH-6) for the prevention of TB. RPT is a rifamycin-S derivative with antimicrobial activity similar to rifampin, but with a longer half-life. RPT is efficacious in the treatment of non-H IV-related TB, and has been shown in animal models to be a highly promising agent for treating latent TB. We hypothesize that the increased tuberculocidal activity and programmatic advantages of supervised, once- or twice- weekly regimens with rifamycin-based combinations will be more effective than INH-6. We also hypothesize that a continuous course of INH will be more effective than INH-6 because elimination of latent TB will be more thorough and prophylaxis will provide ongoing protection against incident TB infection. By studying TB preventive therapy in a setting of comprehensive HIV care for adults in a developing country setting, we will be able to generate critically important data on alternative therapeutic options for TB control among HIV-infected people that will be applicable throughout the world.

描述：（由申请人提供）结核病 (TB) 继续致人死亡 每年约 200 万人，是 HLV 相关的主要原因 发展中国家的发病率和死亡率。此外，结核病似乎 即使成功，也会导致艾滋病毒疾病更快地进展 治疗，因为活动性结核病通过多种途径导致艾滋病毒复制上调 机制。尽管世界卫生组织提出了一项战略 将治疗活动性结核病作为结核病控制的主要武器 有证据表明需要预防性治疗，特别是在 艾滋病毒负担高的国家。异烟肼 (INH) 和利福平 吡嗪酰胺 (RIF/PZA) 已被证明可有效减少 HIV 感染者、结核菌素阳性人群中结核病的短期发病率较高，但 长期效益尚不明确。此外，结核病预防措施的实施 发展中国家的治疗计划受到多种因素的阻碍。 建立临床基础设施以提供预防性治疗， 对坚持治疗方案的担忧，以及很有可能 再次感染随后增加原发性结核病的风险被认为是 不针对艾滋病毒感染者实施预防计划的原因。这 该试验的目的是确定三种新颖的有效性 治疗对艾滋病毒感染成人人群中结核病风险的影响 南非索韦托的临床护理和随访。我们将随机分配 1141 患有艾滋病毒感染且每周接受一次反应性结核菌素皮试的成年人 利福喷汀和 INH (RPT/INH) 持续 12 周，每周两次利福平和 吡嗪酰胺 (RIFIPZA) 8 周，无限期每天连续使用 INH (INH-C)， 或国际公认的六个月每日 INH 标准 (INH-6) 用于预防结核病。 RPT是一种利福霉素-S衍生物，具有抗菌作用 活性与利福平相似，但半衰期更长。 RPT有效 治疗非 HIV 相关结核病，并已在动物模型中显示 是治疗潜伏性结核病的一种非常有前途的药物。我们假设 增加了杀结核菌活性和受监督的规划优势， 每周一次或两次以利福霉素为基础的联合治疗方案会更有效 比 INH-6 更有效。我们还假设持续服用 INH 会 比 INH-6 更有效，因为可以更有效地消除潜伏结核病 彻底的预防将为结核病事件提供持续的保护 感染。通过研究在全面艾滋病毒背景下的结核病预防治疗 照顾发展中国家的成年人，我们将能够产生 关于结核病控制替代治疗方案的极其重要的数据 在艾滋病毒感染者中，这将适用于全世界。