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.

在撒哈拉以南非洲的艾滋病毒感染的恶性并发症中，是最常见的癌症之一 前艺术时代 - 卡波西的肉瘤（KS） - 仍然是艺术时代最常见的。 随着非洲KS的持续事件，新问题和其他尚未尚未 解决。在过去的四年中，在U54 CA190153期间，在乌干达和肯尼亚，我们有 记录了两个令人不安的（及相关）发现：KS诊断时疾病的高级阶段 生存不佳。最近的“全部”（用于艺术）和国家综合癌症网络（NCCN） 化学疗法）现在已经制定了指南，这些结果会改变吗？一个长期存在的问题是为什么 KS发生在HIV感染中？低CD4+ T细胞计数和高血浆HIV RNA是已知的确定剂 未经治疗的艾滋病毒感染，但对于KS来说既不需要也不足够。在诊断领域， 诊断的延迟有许多表现。那，KS诊断会更快吗？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改善生存？ 解决上述问题的每个问题都有一个共同的要求迅速访问患者 最近被诊断为KS。据我们所知，在U54 CA190153的过程中 当我们学习KS时，非洲的癌症的快速案例确定性（RCA）首次使用。 RCA迅速识别 最近被诊断出患有病情的人，在更改之前进行详细测量 疾病，死亡或随访的损失。当前建议中，我们的总体目标是使用RCA回答 关于艺术时代KS的相关临床，流行病学和翻译问题。我们的目标是： AIM 1：监测HIV感染的成年人ART擦除中KS的关键流行病学参数 在东非，特别是KS诊断和生存时疾病的阶段。 AIM 2：评估两名未经ART治疗的HIV患者的入射KS的生物确定剂 以及具有艺术介导的病毒学抑制的人。 AIM 3：评估皮肤病变数字摄影的预测准确性，再加上深 学习算法，以区分KS和非克斯模仿者。 目标4：确定“患者导航”的影响，旨在增强与肿瘤学的联系 诊断为KS的人的护理，以改善KS诊断后的生存。 为了解决这些目标，我们将利用乌干达，肯尼亚和坦桑尼亚和田野的皮肤活检服务 我们在U54 CA190153中获得了经验，以对所有被诊断为KS的患者进行RCA 以及一个构想良好且新颖的“测试阴性”对照组。调查结果将为目标提供努力 控制KS；提高我们对艺术时代KS发病机理的理解；并评估小说 KS诊断策略和新诊断为KS癌症护理的患者的连锁。