Project 2: Rapid Case Ascertainment as a Tool for Epidemiologic Investigation and Efficient Linkage to Care in HIV-infected Patients Diagnosed with Kaposi Sarcoma in East Africa

项目 2：快速病例查明作为东非诊断为卡波西肉瘤的艾滋病毒感染者的流行病学调查和有效护理联系的工具

• 批准号: 10084692
• 负责人: AGGREY SEMWENDERO SEMEERE
• 金额: $ 20.27万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10084692
• 关键词: AIDS related cancer; Address; Adult; Africa; Africa South of the Sahara; African; Algorithms; Biological; Biological Markers; Biopsy; CD4 Positive T Lymphocytes; Caring; Cell Count; Cervical dysplasia; Cessation of life; Clinic; Collection; Control Groups; Coupled; Data; Development; Diagnosis; Digital Photography; Disease; Early Diagnosis; Epidemiology; Evaluation; Funding; Geographic Locations; Goals; Guidelines; HIV; HIV Infections; Human Herpesvirus 8; Image; Incidence; Inflammation; Institution; Intervention; Kaposi Sarcoma; Kenya; Leadership; Link; Localized Malignant Neoplasm; Malignant - descriptor; Malignant Neoplasms; Measurement; Mediating; Mentorship; Monitor; National Comprehensive Cancer Network; Newly Diagnosed; Outcome; Participant; Pathogenesis; Patient imaging; Patients; Persons; Plasma; Prevention; Process; RNA; Reporting; Research; Research Personnel; Research Project Grants; Resources; Role; Scientist; Services; Skin; Tanzania; Techniques; Testing; Time; Uganda; United States; advanced disease; antiretroviral therapy; base; cancer care; career development; chemotherapy; clinically relevant; deep learning algorithm; epidemiology study; experience; follow-up; immune activation; improved; novel; novel strategies; oncology service; rapid diagnosis; skin lesion; tool; virology; virus related cancer

Among malignant complications of HIV infection in sub-Saharan Africa, one of the most common cancers in the pre-ART era — Kaposi’s sarcoma (KS) — continues to be amongst the most common in the ART era. With continued incidence of KS in Africa comes both new questions and others that are still not yet resolved. In the last 4 years in Uganda and Kenya during the course of U54 CA190153, we have documented two disturbing (and related) findings: advanced stage of disease at time of KS diagnosis and poor survival. With recent “Treat All” (for ART) and National Comprehensive Cancer Network (NCCN, for chemotherapy) guidelines now in place, will these outcomes change? A long-standing question is why does KS occur in HIV infection? Low CD4+ T cell count and high plasma HIV RNA are known determinants in untreated HIV infection, but these are neither necessary nor sufficient for KS. In the realm of diagnosis, delays in diagnosis have many manifestations. Thus, can KS diagnosis be more rapid? Finally, can simple interventions that help patients diagnosed with KS navigate to cancer care improve survival? Addressing each of the above questions has one common requirement  swift access to patients recently diagnosed with KS. During the course of U54 CA190153, we implemented, to our knowledge, the first use of rapid case ascertainment (RCA) for cancer in Africa when we studied KS. RCA rapidly identifies persons recently diagnosed with a condition and performs detailed measurements prior to change in disease, death or loss to follow-up. Our overall objective in the current proposal is to use RCA to answer relevant clinical, epidemiologic and translational questions about KS in the ART era. Our Aims are to: Aim 1: Monitor critical epidemiologic parameters of KS in the ART era among HIV-infected adults in East Africa, specifically stage of disease at time of KS diagnosis and survival. Aim 2: Evaluate biologic determinants of incident KS in both ART-untreated HIV-infected patients as well as those with ART-mediated virologic suppression. Aim 3: Assess the predictive accuracy of digital photography of skin lesions, coupled with deep learning algorithms, to distinguish KS from non-KS mimickers. Aim 4: Determine the impact of “patient navigation”, intended to enhance linkage to oncologic care in persons diagnosed with KS, on improving survival after KS diagnosis. To address these aims, we will leverage skin biopsy services in Uganda, Kenya and Tanzania and the field experience we have gained in U54 CA190153 to perform RCA on all patients with newly diagnosed KS as well as a well-conceived and novel “test negative” control group. Findings will inform efforts aimed at controlling KS; improve our understanding of the pathogenesis of KS in the ART era; and evaluate novel strategies for KS diagnosis and linkage of patients newly diagnosed with KS to cancer care.

在撒哈拉以南非洲地区艾滋病毒感染的恶性并发症中，最常见的癌症之一 前 ART 时代——卡波西肉瘤 (KS)——仍然是 ART 时代最常见的疾病之一。 随着非洲 KS 发病率的持续上升，出现了新的问题和其他尚未解决的问题 过去 4 年在乌干达和肯尼亚进行 U54 CA190153 期间，我们已经解决了。 记录了两个令人不安的（和相关的）发现： KS 诊断时疾病处于晚期阶段和 最近的“Treat All”（针对 ART）和国家综合癌症网络（NCCN，针对 ART）的生存率较差。 化疗）指南现已制定，这些结果会改变吗？一个长期存在的问题是为什么会改变？ KS 发生在 HIV 感染中吗？低 CD4+ T 细胞计数和高血浆 HIV RNA 是已知的决定因素 未经治疗的 HIV 感染，但这些对于 KS 诊断来说既不是必要的也不是充分的。 延误诊断有多种表现。那么，KS诊断能否更快速呢？ 帮助诊断为 KS 的患者接受癌症治疗的干预措施可提高生存率？ 解决上述每一个问题都有一个共同的要求：快速接触患者 最近被诊断患有 KS。据我们所知，在 U54 CA190153 的治疗过程中，我们实施了 当我们研究 RCA 快速识别时，在非洲首次使用快速病例查明 (RCA)。 最近被诊断出患有某种疾病并在改变之前进行详细测量的人 我们当前提案的总体目标是使用 RCA 来回答。 ART 时代有关 KS 的相关临床、流行病学和转化问题我们的目标是： 目标 1：监测 ART 时代 HIV 感染成人中 KS 的关键流行病学参数 在东非，特别是 KS 诊断时的疾病阶段和生存期。 目标 2：评估未经 ART 治疗的 HIV 感染患者发生 KS 的生物学决定因素 以及那些通过 ART 介导的病毒学抑制的患者。 目标 3：评估皮肤病变数码摄影结合深度图像的预测准确性 学习算法，以区分 KS 和非 KS 模仿者。 目标 4：确定“患者导航”的影响，旨在加强与肿瘤学的联系 对诊断为 KS 的患者进行护理，以提高 KS 诊断后的生存率。 为了实现这些目标，我们将利用乌干达、肯尼亚和坦桑尼亚的皮肤活检服务以及现场 我们在 U54 CA190153 中获得的经验是对所有新诊断的 KS 患者进行 RCA 以及一个精心设计的新颖的“测试阴性”对照组的研究结果将为旨在实现这一目标的努力提供信息。 控制 KS；提高我们对 ART 时代 KS 发病机制的认识并评估新的方法； KS 诊断策略以及新诊断为 KS 的患者与癌症治疗的联系。