Biomarker and Analytical Core

提议在乌干达马凯雷雷大学和约翰霍普金斯大学之间就艾滋病和肝细胞癌（HCC）建立合作伙伴关系：H2U联盟。肝细胞癌（HCC）在非洲是一种非常常见和致命的癌症，随着HIV患者寿命的延长，HCC的负担将会增加。该联盟的总体目标是减轻撒哈拉以南非洲地区hiv相关HCC的沉重负担。在长期合作的基础上，该联盟的扩展将回答有关艾滋病毒相关HCC的基本流行病学和病因学方面尚未解决的高优先级问题，同时扩大乌干达的临床和实验室研究能力，以解决这些问题。具体目标包括：1)提高乌干达研究者开展hiv相关HCC高水平、协作性、多学科科学调查的能力；2)巩固临床、人口和转化研究基础设施；3)促进对hiv相关HCC的流行病学、发病机制和临床谱的基础认识；4)在资源有限的情况下，提供适用于hiv相关HCC的预防和治疗策略。我们提出了两个主要的临床项目，包括600例HCC病例的大型病例对照研究和600例对照研究，以确定HIV和相关免疫抑制的作用。我们还将对3000名hiv感染的临床患者进行恶性前肝硬化、高危乙型肝炎和黄曲霉毒素相关生物标志物的筛查，然后对这些高危人群进行定期HCC筛查，以确定早期HCC的可行性和是否可以识别。我们的发展核心将实施H2U学者奖，将一名乌干达研究者与霍普金斯大学的一名高级导师配对，并支持职业发展和一个合作试点项目。拟议的研究将加强我们对HIV相关HCC的临床和机制的理解，为适当的治疗提供证据，并为非洲防治HIV和HCC的干预策略提供信息。我们的综合研究和能力发展活动的影响将是建立H2U联盟，作为非洲艾滋病毒和HCC的卓越中心。

Proposed is a collaborative partnership between Makerere University and Johns Hopkins on HIV and hepatocellular carcinoma (HCC) in Uganda: The H2U Consortium. Hepatocellular carcinoma (HCC) is a very common and lethal cancer in Africa, and as patients with HIV live longer, the HCC burden will increase. The overarching goal of the Consortium is to reduce the heavy burden of HIV-associated HCC in sub-Saharan Africa. Building on long-standing collaborations, the Consortium expands will answer unresolved, high priority questions on the fundamental epidemiology and etiology of HIV-associated HCC, while expanding the clinical and laboratory research capacity in Uganda to address these issues. The Specific Aims include: 1) To enhance Ugandan investigator capacity for conducting high-level, collaborative, multidisciplinary scientific investigation of HIV-associated HCC; 2) To solidify the clinical, population and translational research infrastructure; 3) To advance the foundational understanding of the epidemiology, mechanisms, and clinical spectrum of HIV-associated HCC; and 4)To inform prevention and treatment strategies applicable to HIV-associated HCC in resource-limited settings. We propose two major clinical projects, including a large case-control study of 600 HCC cases and 600 controls to define the role of HIV and related immunosuppression. We also will screen 3000 HIV-infected clinic patients for pre-malignant liver cirrhosis and for high-risk hepatitis B and aflatoxin-related biomarkers, then follow this high-risk group with regular HCC screening to determine feasibility and whether early stage HCC can be identified. Our Developmental Core will implement the H2U Scholars Award, pairing a Ugandan investigator with a senior Hopkins mentor and supporting career development and a collaborative pilot project. The proposed studies will enhance our clinical and mechanistic understanding of HIV-associated HCC, provide evidence on appropriate treatment, and inform intervention strategies to combat HIV and HCC in Africa. The impact of our integrated research and capacity development activities will be establishment of the H2U Consortium as a Center of Excellence on HIV and HCC in Africa.