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

摘要 卡波西氏肉瘤(KS)在撒哈拉以南非洲地区仍然是一种高度流行的恶性肿瘤。抗逆转录病毒治疗 (ART)和相关的免疫重建与急性髓细胞白血病患病率的显著下降相关。 在美国艾滋病毒感染人群中发现了KS，但抗逆转录病毒疗法对撒哈拉以南非洲地区KS的影响还不太清楚。在……里面 在赞比亚，即使抗逆转录病毒治疗的规模扩大，KS仍然是成年男性中第二常见的癌症。为 在女性中，这是第三常见的。KS的早期识别和明确诊断的管道和 耐受性好并将副作用降至最低的适当治疗是一种基本的策略，可以 在赞比亚实施，并将改善KS患者的预后。此应用程序的总体目标是 在赞比亚实施一项战略，以早期识别和诊断KS，并将诊断与预期结合起来 抗逆转录病毒治疗成败的深层原因探究(S)。项目团队 假设HIV和KSHV病毒载量、遗传和可溶性蛋白等因素或免疫学因素 对KS患者应用ART之前的参数影响早期KS治疗的结果 单单是艺术。这些危险因素的识别可以作为指导KS治疗的预后标志。 决定(谁只接受ART治疗，以及谁接受ART/化疗)，并将增进对 早期KS病的发病机制。这些活动将有助于改进早期识别和最终确定 诊断出一种与艾滋病相关的主要恶性肿瘤。这些改进，加上风险因素和 预后生物标记物的鉴定，反过来将改善HIV+KS患者的预后和治疗 赞比亚和整个撒哈拉以南非洲。这最终将有助于更好地理解KS 发病机制和开发新的干预策略。

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.