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

描述（申请人提供）：南非夸祖鲁纳塔尔省德班是全球艾滋病毒流行的中心，大量感染艾滋病毒的人也同时感染了结核病。MRC临床试验单位（MRC CTU）因开展大规模艾滋病毒预防试验而享誉国际，包括杀微生物剂，阴道隔膜和口服暴露前预防（PrEP）；艾滋病治疗试验和社会行为研究。6个完善的临床研究点位于大德班地区，年轻妇女的艾滋病毒发病率从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认识表明，需要对艾滋病毒和结核病的预防、治疗以及与护理的联系采取综合办法。MRC CTU的主要目标是通过与4个网络合作，整合现场操作、社区伙伴关系和对依从性挑战/行为研究的响应，以实现以下目标：目标1：在高危人群中开展长效杀微生物剂、口服PrEP和艾滋病毒疫苗的艾滋病毒预防试验。我们假设长效制剂在这一人群中可以规避依从性挑战。目标2：开展新颖、安全、有效和稳健的治疗试验。我们假设，在可预见的未来，在我们的环境中，将需要具有成本效益的三线治疗方案。目的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利用分子诊断确定耐多药结核病治疗时间和优化药物方案的试验来解决结核病治疗方面的重大差距。目标4：防治艾滋病的综合战略。没有任何单一的艾滋病毒预防办法能够解决这一流行病。我们希望参与艾滋病毒预防综合战略的试验，以及那些综合战略

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. RELEVANCE: This comprehensive attempt to address the dual HIV/TB pandemic in Durban, South Africa through an integrated approach of testing novel HIV prevention strategies, novel HIV therapeutics agents for future options, and addressing HIV co-morbidity with TB with appropriate linkage to care, will provide the empirical data to guide future real-world development and implementation of effective HIV and TB strategies.