Implementing HIV/Cervical Cancer Prevention CASCADE Clinical Trials in Zimbabwe (ZIM-CASCADE)

项目摘要/摘要 津巴布韦是一个资源有限的国家，艾滋病毒和宫颈癌(CXCA)负担很重。 津巴布韦患有CXCA的妇女患有晚期疾病，三分之二的人在确诊后一年内死亡。 CXCA筛查覆盖率低(13%)，主要通过醋酸目视检查进行 (VIA)，计划迁移到人类乳头瘤病毒(HPV)脱氧核糖核酸(DNA)检测。癌前病变 治疗主要是冷冻或热消融，但只有53%的筛查阳性女性可以接受治疗。至 达到世界卫生组织2030年的目标，即在2120年前消除CXCA，津巴布韦需要新的干预措施，包括 可接受、负担得起、护理点、可扩展且经临床验证。优化CXCA筛查和前处理 加州大学旧金山分校(UCSF)艾滋病毒携带者(WLWH)癌症治疗级联 和津巴布韦大学-临床试验研究中心(CTRC)，与当地的PEPFAR合作- 公共卫生干预与发展组织(OPHID)和 津巴布韦卫生技术援助、培训和教育中心(ZIM-TTech)(统称， ZIM-CASCADE)建议作为LMIC CASCADE UG1临床站点。ZIM-CASCADE借鉴 在WLWH的临床研究和CXCA筛查和治疗方面具有丰富的经验， 获得95,000 WLWH，其中44,000人目前正在接受全面的CXCA筛查和 通过位于津巴布韦高密度人口的OPHID和ZIM-TTech方案进行治疗 哈拉雷和奇通威扎的中心。ZIM-CASCADE将由全球2名妇科肿瘤学家领导 在CXCA筛查和治疗方面的公认专业知识，并将利用研究人员和基础设施 来自专门的临床研究站点和以社区为基础的初级保健诊所，他们的经验是 经过近30年的持续研究活动发展起来的。ZIM-CASCADE将参与所有4项 级联网络的科学重点领域，将完成以下具体目标：(1)提供 通过借鉴广泛的临床专业知识来洞察计划试验的临床意义和可行性 WLWH人群CXCA预防；(2)利用扩展的多功能基础设施和研究管理 经过28年开发的系统，以进行高质量的实用临床试验；(3)积累和保留合格的 WLWH通过与社区合作伙伴有效和公平地接触；以及(4)确保遵守 所有方案程序和适用的研究规则。完成这些目标将做出至关重要的贡献 优化、实施和扩大有效的宫颈癌预防的证据 在资源有限的情况下对WLWH的干预，多模式级联数据将告知公众 津巴布韦和全球的卫生政策。

Project Summary/Abstract Zimbabwe is a resource-constrained country with a high burden of HIV and cervical cancer (CXCA). Zimbabwean women with CXCA present with advanced disease and two-thirds die within a year of diagnosis. CXCA screening has low coverage (13%), and is conducted largely through visual inspection with acetic acid (VIA), with plans to migrate to human papillomavirus (HPV) deoxyribonucleic acid (DNA) testing. Precancer treatment is mostly cryotherapy or thermal ablation but is only accessed by 53% of women screen positive. To meet the WHO 2030 target of eliminating CXCA by 2120, Zimbabwe needs new interventions that are acceptable, affordable, point-of-care, scalable, and clinically proven. To optimize CXCA screening and the pre- cancer treatment cascade for women living with HIV (WLWH), University of California, San Francisco (UCSF) and the University of Zimbabwe–Clinical Trials Research Centre (CTRC), in collaboration with local PEPFAR- funded implementation partners Organization for Public Health Interventions and Development (OPHID) and the Zimbabwe Technical Assistance, Training and Education Center for Health (Zim-TTECH) (collectively, ZIM-CASCADE) propose to serve as a LMIC CASCADE UG1 Clinical Site. ZIM-CASCADE draws on extensive experience in conducting clinical research and CXCA screening and treatment among WLWH, with access to 95,000 WLWH, of whom >44,000 are currently receiving comprehensive CXCA screening and treatment through the OPHID and Zim-TTECH programs located in Zimbabwe’s high-density population centers of Harare and Chitungwiza. ZIM-CASCADE will be led by 2 gynecological oncologists with globally recognized expertise in CXCA screening and treatment and will utilize research personnel and infrastructure from dedicated clinical research sites and community-based primary care clinics, whose experience has been developed over nearly 3 decades of continuous research activities. ZIM-CASCADE will participate in all 4 scientific focus areas of the CASCADE Network, and will complete the following Specific Aims: (1) Provide insight as to clinical significance and feasibility of planned trials by drawing on extensive clinical expertise in CXCA prevention among WLWH; (2) Utilize the expansive pluripotent infrastructure and research management systems developed over 28 years to conduct high quality pragmatic clinical trials; (3) Accrue and retain eligible WLWH through effective and equitable engagement with community partners; and (4) Ensure compliance with all protocol procedures and applicable research regulations. Completion of the Aims will contribute critical evidence to inform optimization, implementation, and scale-up of effective cervical cancer prevention interventions for WLWH in resource-limited settings, and the multi-modal CASCADE data will inform public health policy in Zimbabwe and globally.