Biomarkers of Kaposi sarcoma recrudescence in Zambia

赞比亚卡波西肉瘤复发的生物标志物

• 批准号: 10652768
• 负责人: Owen Ngalamika
• 金额: $ 4.1万
• 依托单位: UNIVERSITY OF ZAMBIA
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-16 至 2024-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10652768
• 关键词: AIDS with Kaposi' s sarcoma; Adult; Africa South of the Sahara; Biological Markers; Development; Disease remission; HIV; Human Herpesvirus 8; Immune response; Immunologics; In complete remission; Individual; Intervention; Kaposi Sarcoma; Lesion; Maintenance Therapy; Malignant Neoplasms; Outcome; Pathogenesis; Patient Selection; Patients; Population; Predictive Value; Prevalence; Recrudescences; Recurrence; Testing; Viral; Woman; Zambia; antiretroviral therapy; biomarker identification; chemotherapy; cohort; experience; follow-up; high risk; immune reconstitution; improved; men; novel; prognostic value; prospective; scale up

ABSTRACT Kaposi's sarcoma (KS) remains a highly prevalent malignancy in sub-Saharan Africa. Antiretroviral therapy (ART) and associated immune reconstitution has been correlated with a dramatic decline in the prevalence of KS in the US 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. Furthermore, treatment with chemotherapy plus ART is associated with recurrence rates of up to 50 percent in those that have a complete response. The overall objective of this application is to identify markers of epidemic KS recurrence and/or sustained remission in individuals that have an initial complete regression of lesions upon chemotherapy. We hypothesize that individuals with complete regression of all the lesions after chemotherapy will have differences in immunological and viral factors that have prognostic value for predicting KS re-development and/or sustained remission. We will test our hypothesis by longitudinally characterizing innate, humoral, and cellular immune responses against KSHV and comparing individuals that experience recurrence to those who do not. The identification of these biomarkers of outcome after remission will enable the selection of patients that require a longer follow up period, those that require maintenance therapy, and those that require second line chemotherapy. From our proposed activities, we will improve the long-term outcomes of HIV+ individuals that have had KS before and hence at high risk of recurrence. This will ultimately inform efforts to better understand KS pathogenesis and develop novel interventional strategies.

摘要