Research Project 1: Epidemiology of Kaposi's Sarcoma and Kaposi's Sarcoma-Associated Herpesvirus

研究项目1：卡波西肉瘤和卡波西肉瘤相关疱疹病毒的流行病学

• 批准号: 9404824
• 负责人: Owen Ngalamika
• 金额: $ 10.99万
• 依托单位: UNIVERSITY OF NEBRASKA LINCOLN
• 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/9404824
• 关键词: Acquired Immunodeficiency Syndrome; Adult; Adverse effects; Africa South of the Sahara; Anti-Retroviral Agents; Biopsy Specimen; Cells; Child; Client; Clinical; Country; Coupled; Diagnosis; Disease; Disease remission; Early identification; Early treatment; Education; Educational workshop; Epidemiology; Failure; Genetic; Goals; HIV; HIV-1; HIV-1 drug resistance; Herpesviridae; Human; Human Herpesvirus 8; Immune; Immunohistochemistry; Immunologic Markers; Immunologics; Intervention; Investigation; Kaposi Sarcoma; Latent Virus; Malignant Neoplasms; Measures; Mediating; Monoclonal Antibodies; Newly Diagnosed; Outcome; Pathogenesis; Patients; Pattern; Plasma; Population; Prevalence; Prognostic Marker; Proteins; Research Project Grants; Risk; Risk Factors; Saliva; Sampling; Testing; Training; Treatment outcome; Viral Load result; Virus Diseases; Woman; Zambia; antiretroviral therapy; biomarker identification; cell mediated immune response; chemotherapy; cytotoxicity; early childhood; follow-up; improved; improved outcome; latency-associated nuclear antigen; men; novel; outcome forecast; programs; prospective; reconstitution; responders and non-responders; scale up; screening; success; treatment responders

ABSTRACT Kaposi's sarcoma (KS) remains a highly prevalent malignancy in sub-Saharan Africa. Anti-retroviral therapy (ART) and associated immune reconstitution has been correlated with a dramatic decline in the prevalence of KS in the U.S. HIV-infected population, but the impact of ART on KS in sub-Saharan Africa is less clear. In Zambia, even with the scale up of ART, KS remains the second most common cancer among adult men. For women, it is the third most common. Early identification of KS and a pipeline to definitive diagnosis and appropriate treatments that are well-tolerated and minimize side-effects is an essential strategy that can be implemented in Zambia and will improve outcomes for KS patients. The overall goals of this application are to implement a strategy in Zambia to identify and diagnose KS early and couple diagnosis to prospective investigations of the underlying cause(s) of ART treatment successes and failures. The project team hypothesizes that factors such as HIV and KSHV viral load, genetics, and soluble proteins, or immunological parameters that preexist the administration of ART to KS patients impact the outcome of early KS therapy with ART alone. The identification of these risk factors can serve as prognostic markers for directing KS treatment decisions (whom to treat with ART alone, and whom with ART/chemo), and will enhance understanding of early KS disease pathogenesis. These activities will result in improved early identification and definitive diagnosis of a major AIDS-associated malignancy. These improvements, coupled with the risk factor and prognostic biomarker identification, will, in turn, improve the prognosis of and treatment of HIV+ KS patients in Zambia and throughout sub-Saharan Africa. This will ultimately inform efforts to better understand KS pathogenesis and develop novel interventional strategies.

摘要 卡波西肉瘤（KS）仍然是撒哈拉以南非洲地区的一种高度流行的恶性肿瘤。抗逆转录病毒疗法 (ART)以及相关的免疫重建与以下疾病的患病率急剧下降有关： KS在美国的艾滋病毒感染人群中，但ART对KS在撒哈拉以南非洲的影响不太清楚。在 在赞比亚，即使ART的规模扩大，KS仍然是成年男性中第二常见的癌症。为 女性，这是第三常见的。KS的早期识别和明确诊断的管道， 耐受性良好并将副作用降至最低的适当治疗是一种基本策略， 在赞比亚实施，将改善KS患者的结局。此应用程序的总体目标是 在赞比亚实施一项战略，以便早期发现和诊断KS，并将诊断与预期的 调查ART治疗成功和失败的根本原因。项目组 假设HIV和KSHV病毒载量、遗传学和可溶性蛋白质或免疫学等因素 KS患者ART给药前存在的参数影响早期KS治疗的结果， 艺术独自这些危险因素的识别可以作为指导KS治疗的预后指标 决定（谁只与艺术治疗，谁与艺术/化疗），并将加强了解， KS病早期发病机制。这些活动将改善早期识别和确定 诊断为主要的艾滋病相关恶性肿瘤。这些改进，加上风险因素， 预后生物标志物的鉴定，将反过来改善HIV+ KS患者的预后和治疗， 赞比亚和整个撒哈拉以南非洲。这将最终为更好地了解KS的努力提供信息 发病机制和开发新的干预策略。