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

项目概要/摘要 乌干达是艾滋病毒感染妇女宫颈癌（CXCA）负担最高的8个国家之一 （WLWH），艾滋病毒可归因的年龄标准化发病率为每10万人10-20人。宫颈癌的治疗策略 癌症（CXCA）预防包括有针对性的人乳头瘤病毒（HPV）疫苗接种， 25-49岁，通过醋酸（VIA）或HPV DNA检测进行目视检查， 冷冻疗法或消融。然而，CXCA干预措施的可用性和可获得性有限且稀少 这是由于“筛查和治疗”策略的低吸收而加剧的。可扩展、经济实惠、即时、临床 经证实的新型干预措施（包括HPV自我采样技术、HPV分子生物标志物检测、癌前病变 诊断和成像技术以及消融和切除治疗）是必要的。此夕h 这些新的经临床证实的干预措施的有效性仍然未知，这限制了 美国和中低收入国家（LMIC）的预期使用环境。支持正在进行的努力， 推出新的筛选和治疗策略，马凯雷雷大学沃尔特里德项目（MUWRP）合作 与美国军方艾滋病毒研究计划（MHRP）提出参加艾滋病毒/宫颈癌 预防“CASCADE”临床试验网络作为UG 1临床研究中心（UG 1 CRS）实施 在乌干达进行的临床试验我们将：1）利用MUWRP在临床试验方面的专业知识和经验， WLWH中的CXCA预防，为研究可行性和临床意义提供有价值的见解和输入 在概念和方案制定过程中考虑当地情况; 2）及时累积CASCADE目标， 保留≥ 95%的研究参与者，利用MUWRP的多能性经验、临床研究基础设施 和资源;以及3）提供称职的领导，以确保程序忠实于方案和所有适用的 条例和准则。MUWRP还将支持UG 1研究基地和U24协调中心， 获得CASCADE试验的伦理和监管批准，并忠实地执行临床试验方案。 MUWRP是UG 1 CRS的理想和合理选择，因为MUWRP具有：1）在 城市、半城市和农村地区的114个卫生设施，由MUWRP的综合艾滋病毒/艾滋病方案提供支持 乌干达中部预防、护理和治疗（CARE）计划由美国总统紧急援助基金资助 艾滋病救援计划（PEPFAR）; 2）开展艾滋病毒临床研究和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计划;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， 其他LMIC MUWRP的专业知识和能力将支持CASCADE的所有四个研究重点领域 网络MUWRP和MHRP将生成最终告知CXCA政策和筛查及治疗的证据 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.