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: 10907940
• 负责人: AGGREY SEMWENDERO SEMEERE
• 金额: $ 12.45万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-13 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10907940
• 关键词: 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; Epidemiology; Evaluation; Funding; Geographic Locations; Geography; Goals; Guidelines; HIV; HIV Infections; Human Herpesvirus 8; Image; Incidence; Institution; Intervention; Kaposi Sarcoma; Kenya; Leadership; Liberia; Link; Localized Malignant Neoplasm; Malignant - descriptor; Malignant Neoplasms; Measurement; Mediating; Mentors; Mentorship; Monitor; National Comprehensive Cancer Network; Newly Diagnosed; Outcome; Participant; Pathogenesis; Patient imaging; Patients; Persons; Photography; Plasma; Process; Public Health; RNA; Reporting; Research; Research Personnel; Research Project Grants; Resources; Role; Scientist; Services; Skin; Tanzania; Techniques; Testing; Time; Uganda; advanced disease; antiretroviral therapy; cancer care; cervical cancer prevention; chemotherapy; clinically relevant; deep learning algorithm; epidemiology study; experience; follow-up; immune activation; improved; novel; novel strategies; oncology service; patient navigation; rapid diagnosis; skin lesion; systemic inflammatory response; tool

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.

在撒哈拉以南非洲艾滋病毒感染的恶性并发症中，非洲最常见的癌症之一是癌症。 ART前时代-卡波西肉瘤（KS）-仍然是ART时代最常见的肿瘤之一。 随着KS在非洲的持续发生，出现了新的问题和其他尚未解决的问题 解决了在乌干达和肯尼亚的U 54 CA 190153课程的过去4年中， 记录了两个令人不安的（和相关的）发现：在KS诊断时疾病的晚期， 可怜的生存。随着最近的“治疗所有”（ART）和国家综合癌症网络（NCCN， 化疗）指南，这些结果会改变吗？一个长期存在的问题是， KS是否会发生在HIV感染者身上？低CD 4 + T细胞计数和高血浆HIV RNA是HIV感染的已知决定因素。 未经治疗的艾滋病毒感染，但这些既不是必要的，也不是足够的KS。在诊断领域， 延误诊断有多种表现。那么，KS的诊断能不能更快呢？最后，可以简单 帮助诊断为KS的患者导航到癌症护理的干预措施可以提高生存率？ 解决上述每个问题都有一个共同的要求，即快速接触患者 最近被诊断为KS。在U 54 CA 190153课程期间，据我们所知， 在研究KS时，我们在非洲首次使用快速病例确定（RCA）治疗癌症。RCA快速识别 最近被诊断出患有某种疾病的人，并在改变之前进行详细的测量。 疾病、死亡或失访。我们在当前提案中的总体目标是使用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： 目的1：监测艾滋病毒感染成人中抗逆转录病毒治疗时期KS的关键流行病学参数 在东非，特别是在KS诊断和存活时疾病分期。 目的2：评价ART治疗的HIV感染患者中偶发KS的生物学决定因素 以及ART介导的病毒学抑制。 目的3：评估皮肤病变的数字摄影的预测准确性， 学习算法，以区分KS与非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，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， 我们在U 54 CA 190153中获得了对所有新诊断KS患者进行RCA的经验， 以及一个构思良好的新颖的“阴性试验”对照组。调查结果将为旨在 控制KS;提高我们对ART时代KS发病机制的理解;并评估新的 KS诊断策略和新诊断KS患者与癌症护理的联系。