Implementing HIV/Cervical Cancer Prevention CASCADE Clinical Trials in Uganda (CASCADE UGANDA)

项目摘要/摘要 在感染艾滋病毒的妇女中，乌干达是宫颈癌负担最重的8个国家之一 (WLWH)，艾滋病毒可归因于年龄标准化发病率为每10万人中有10-20人。治疗宫颈疾病的策略 癌症(CXCA)预防包括有针对性的人乳头瘤病毒(HPV)疫苗接种，对老年妇女进行筛查 25-49岁，通过醋酸(VIA)或HPV DNA检测进行目测，并通过以下方式进行癌症前治疗 冷冻治疗或消融。然而，CXCA干预措施的可获得性和可获得性有限且稀少 而对“筛查和治疗”策略的接受程度较低，更是雪上加霜。临床上可扩展、经济实惠的医疗保健点 经过验证的新干预措施(包括HPV自我采样技术、HPV分子生物标记物检测、癌前病变 诊断和成像技术，以及消融和切除治疗)势在必行。此外， 这些新的经临床证实的干预措施的有效性仍不清楚，这限制了在 美国和中低收入国家(LMIC)的目标使用环境。支持正在进行的努力 与Makerere大学沃尔特·里德项目(MUWRP)合作推出新的筛查和治疗策略 与美国军方艾滋病毒研究计划(MHRP)提议参与艾滋病毒/宫颈癌 作为UG1临床研究站点(UG1 CRS)实施的预防“级联”临床试验网络 在乌干达进行务实的临床试验。我们将：1)利用MUWRP在临床试验和 为WLWH人群CXCA预防研究的可行性、临床意义提供有价值的见解和意见 在概念和协议开发过程中的本地上下文；2)及时积累级联目标和 保留≥95%的研究参与者利用MUWRP的多功能经验、临床研究基础设施 和资源；以及3)提供称职的领导，以确保程序忠于议定书和所有适用的 条例和指导方针。MUWRP还将支持UG1研究基地和U24协调中心 获得级联试验的伦理和监管批准，并忠实地执行临床试验方案。 MUWRP是UG1 CRS的理想而合理的选择，因为MUWRP具有：1)可访问超过37,000千瓦时 城市、半城市和农村环境，114个卫生设施，由妇幼保健部全面艾滋病毒/艾滋病支助 由美国总统紧急情况资助的乌干达中部预防、护理和治疗(CARE)计划 艾滋病救助计划(PEPFAR)；2)进行HIV临床研究和CXCA筛查的丰富经验 和非洲队列研究中的癌前治疗，以及CARE支持的CXCA方案；以及3)国际 在乌干达进行涉及WLWH的临床试验方面具有经验和专业知识的知名科学家和 其他LMIC。水利部的专门知识和能力将支持级联的所有四个研究重点领域 网络。MUWRP和MHRP将生成最终通知CXCA政策和筛查和治疗的证据 WLWH的战略。

PROJECT SUMMARY/ABSTRACT Uganda is one of 8 countries with the highest burden of cervical cancer (CXCA) among women living with HIV (WLWH) with an HIV-attributable age-standardized incidence rate of 10–20 per 100,000. Strategies for Cervical Cancer (CXCA) prevention include targeted Human Papillomavirus (HPV) vaccination, screening of women aged 25-49 years by visual inspection with acetic acid (VIA) or HPV DNA testing, and precancer treatment by cryotherapy or ablation. However, there is limited and sparse availability of and access to CXCA interventions which is compounded by low-uptake of ‘screen and treat’ strategies. Scalable, affordable, point-of-care, clinically proven novel interventions (including HPV self-sampling techniques, HPV molecular biomarker tests, precancer diagnostics and imaging techniques, and ablative and excisional treatments) are imperative. Further, the effectiveness of these novel clinically proven interventions remains unknown which limits implementation in intended-use settings in the US and low- and middle-income countries (LMICs). To support on-going efforts to roll-out novel screen and treat strategies, the Makerere University Walter Reed Project (MUWRP) in partnership with the U.S. Military HIV Research Program (MHRP) propose to participate in the HIV/Cervical Cancer Prevention ‘CASCADE’ Clinical Trials Network as a UG1 Clinical Research Site (UG1 CRS) to implement pragmatic clinical trials in Uganda. We will: 1) leverage MUWRP’s expertise and experience in clinical trials and CXCA prevention among WLWH to provide valuable insight and input on study feasibility, clinical significance and local context during concept and protocol development; 2) accrue CASCADE targets in a timely manner and retain ≥ 95% of study participants leveraging MUWRP’s pluripotent experience, clinical research infrastructure and resources; and 3) provide competent leadership to ensure procedural fidelity to protocols and all applicable regulations and guidelines. MUWRP will also support UG1 Research Bases and U24 Coordination Center to obtain ethical and regulatory approvals for CASCADE trials, and implement clinical trial protocols with fidelity. MUWRP is an ideal and rational choice for a UG1 CRS as MUWRP has: 1) access to over 37,000 WLWH in urban, semi-urban, and rural settings at 114 health facilities supported by MUWRP’s Comprehensive HIV/AIDS Prevention, Care and Treatment in Central Uganda (CARE) program funded by the U.S. President's Emergency Plan for AIDS Relief (PEPFAR); 2) extensive experience conducting HIV clinical research and CXCA screening and precancer treatment in the African Cohort Study, and CARE supported CXCA program; and 3) internationally renowned scientists with experience and expertise in conducting clinical trials involving WLWH in Uganda and other LMICs. MUWRP’s expertise and capacity will support all four research focus areas of the CASCADE Network. MUWRP and MHRP will generate evidence that ultimately informs CXCA policy and screen and treat strategies for WLWH.