South African Medical Research Council Clinical Trials Unit (MRC CTU)

描述(申请人提供)：南非夸祖鲁纳塔尔德班是全球艾滋病毒大流行的震中，那里有大量艾滋病毒感染者也同时感染了结核病。MRC临床试验单位(MRC CTU)以进行大规模的艾滋病毒预防试验而闻名国际，这些试验包括杀菌剂、阴道隔膜和口服暴露前预防(PrEP)、艾滋病毒治疗试验和社会行为研究。6个成熟的临床研究站点(CRSS)位于大德班地区，那里的年轻女性艾滋病毒发病率从5.1/100Py(早期研究)到16.4/100Py(2012年)不等。早期试验缺乏有效性是由于多种因素，包括依从性差。目前对这一流行病的了解表明，需要对艾滋病毒和结核病的预防、治疗和与护理的联系采取综合办法。MRC CTU的主要目标是通过与4个网络公司合作，整合现场运营、社区伙伴关系和对遵守挑战/行为研究的反应，以实现以下目标：目标1：在高危人群中进行长效杀菌剂和口服PrEP和艾滋病毒疫苗的艾滋病毒预防试验。我们假设，在这一人群中，长效配方可能会绕过依从性挑战。目的2：进行新的、安全、有效和可靠的方案的治疗试验。我们假设，在我们的环境中，在可预见的未来将需要具有成本效益的三线治疗方案。目标3：开展HIV相关合并症的随机对照试验。我们建议通过开发和参与试验来解决结核病治疗中的关键空白，利用分子诊断学来确定治疗持续时间并优化耐多药结核病的药物方案。目标4：应对这一流行病的综合战略。任何单一的艾滋病毒预防方案都不能解决这一流行病。我们希望参与测试艾滋病毒预防综合战略以及综合战略的试验。 预防和治疗艾滋病毒和结核病，并与护理有效联系。MRC CTU可以接触到处于危险中的人口、发展完善的中央研究中心基础设施，以及国际顾问的经验和专门知识，以承担和交付拟议的研究目标。

DESCRIPTION (provided by applicant): Durban, KwaZulu Natal, South Africa is the epicenter of the global HIV pandemic, where a large number of people infected with HIV are also co-infected with TB. The MRC Clinical Trials Unit (MRC CTU) is internationally renowned for conducting large scale trials of HIV prevention including microbicides, vaginal diaphragm, and oral Pre-Exposure Prophylaxis (PrEP); HIV therapeutic trials, and socio-behavioral studies. Six well-established clinical research sites (CRSs) are located in the greater Durban area, where HIV incidence among young women ranges from 5.1/100PY (in earlier research) to 16.4/100PY (in 2012). Lack of effectiveness in earlier trials was due to multiple factors, including poor adherence. The current understanding of the epidemic suggests a need for an integrated approach to HIV and TB prevention, treatment, and linkage to care. The MRC CTU's primary goal is to integrate site operations, community partnerships, and responses to adherence challenges/behavioral research by partnering with 4 Networks to meet the following aims: AIM 1: Conduct HIV prevention trials of long-acting microbicides and oral PrEP and HIV vaccines in at-risk populations. We hypothesize that long-acting formulations in this population may circumvent adherence challenges. AIM 2: Conduct therapeutic trials of novel, safe, effective, and robust regimens. We hypothesize that cost-effective, third-line treatment regimens will be needed in the foreseeable future in our setting. AIM 3: To undertake RCTs of HIV-associated co-morbidities. There are critical gaps in TB treatment that we propose to address by developing and participating in trials using molecular diagnostics to determine treatment duration and optimize drug regimens for multidrug-resistant TB. AIM 4: Integrated strategies to address the epidemic. No single HIV prevention option will address the epidemic. We hope to participate in trials testing integrated strategies of HIV prevention, as well as those integrating prevention and treatment of both HIV and TB, with effective linkage to care. The MRC CTU has access to the population at-risk, a well-developed and centralized CRS infrastructure, and the experience and expertise of international consultants to undertake and deliver on the proposed research aims.