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

在撒哈拉以南非洲地区艾滋病毒感染的恶性并发症中， 前艺术时代-卡波西肉瘤(KS)-仍然是艺术时代最常见的肿瘤之一。 随着非洲KS的持续发生，既有新的问题，也有其他尚未出现的问题 解决了。在过去的4年里，在乌干达和肯尼亚的U54 CA190153课程中，我们 记录了两个令人不安的(和相关的)发现：在诊断KS时疾病处于晚期， 生存能力很差。与最近的“治疗所有人”(用于抗逆转录病毒治疗)和国家综合癌症网络(NCCN，用于 化疗)指南现已到位，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感染中吗？低CD4T细胞计数和高血浆HIV RNA是已知的决定因素 未经治疗的艾滋病毒感染，但对KS来说，这些既不是必要的，也不是充分的。在诊断领域， 延误诊断有多种表现。因此，KS的诊断能更快吗？最后，可以简单地 帮助被诊断为KS的患者进入癌症护理以提高存活率的干预措施？ 解决上述每一个问题都有一个共同的要求，即快速接触患者 最近被诊断出患有KS。在U54 CA190153的过程中，据我们所知，我们实施了 当我们研究KS时，第一次在非洲使用了癌症快速病例确定(RCA)。RCA快速识别 最近被诊断出患有某种疾病并在发生变化之前进行详细测量的人 疾病、死亡或失访。我们当前提案的总体目标是使用RCA来回答 关于ART时代KS的相关临床、流行病学和翻译问题。我们的目标是： 目标1：监测艾滋病病毒感染成人中抗逆转录病毒治疗时代KS的关键流行病学参数 在东非，尤其是在确诊为KS并存活时的疾病阶段。 目的2：评估未接受抗逆转录病毒治疗的HIV感染患者中发生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药物。 目标3：评估数字摄影对皮肤病变的预测准确性，结合深度 学习算法，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 对被诊断为KS的患者进行护理，以提高KS诊断后的存活率。 为了实现这些目标，我们将利用乌干达、肯尼亚、坦桑尼亚和实地的皮肤活检服务。 U54 CA190153对所有新诊断的KS AS患者施行RCA的经验 以及一个构思精良、新奇的“测试阴性”对照组。调查结果将为旨在 控制KS；提高我们对艺术时代KS发病机制的理解；评价小说 KS诊断的策略以及新诊断的KS患者与癌症护理的联系。

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.