Immune Reconstitution of HIV-1 Infected Zambian Children Initiating Antiretrovira

描述（由申请人提供）：了解抗逆转录病毒治疗（ART）对在撒哈拉以南非洲开展抗逆转录病毒治疗（ART）的儿童中病原体特异性免疫重建的影响，对HIV-1感染儿童的最佳护理和有效利用稀缺资源至关重要。该建议的第一个长期目标是，以对麻疹病毒的免疫反应为模型，描述撒哈拉以南非洲地区开始抗逆转录病毒治疗的儿童中病原体特异性免疫重建的程度。第二个长期目标是应用免疫记忆理解方面的最新进展来探索ART对儿童记忆T和b淋巴细胞对麻疹病毒免疫反应的影响。第三个长期目标是评估抗逆转录病毒治疗对人群麻疹病毒免疫力的影响，作为撒哈拉以南非洲接受抗逆转录病毒治疗的感染艾滋病毒1型儿童麻疹疫苗再接种决策的依据。在我们对赞比亚卢萨卡感染艾滋病毒的儿童进行麻疹和麻疹疫苗接种研究的基础上，我们将对在赞比亚卢萨卡公共诊所开始抗逆转录病毒治疗的感染艾滋病毒的儿童进行一项前瞻性观察队列研究，以实现以下具体目标：1)描述启动抗逆转录病毒治疗的HIV-1感染赞比亚儿童免疫重建的幅度和质量，并通过测量对麻疹病毒的记忆免疫反应确定病原体特异性免疫重建；2)测量接受抗逆转录病毒治疗且缺乏保护性抗体滴度的hiv -1感染赞比亚儿童在重新接种前后对麻疹病毒的体液和细胞免疫反应；3)利用数学模型评价在HIV-1高流行地区为接受抗逆转录病毒治疗的HIV-1感染儿童重新接种疫苗的政策对消除麻疹的重要性。在有和没有重新接种政策的情况下，将在一个数学模型中使用接受抗逆转录病毒药物治疗的感染艾滋病毒1型儿童在重新接种前后都受到麻疹病毒保护的比例估计数，以评估抗逆转录病毒药物治疗对人口对麻疹病毒免疫的影响。这项研究将流行病学和免疫学研究联系起来，其公共卫生意义在于，通过评估抗逆转录病毒治疗对免疫重建和对疫苗可预防疾病的免疫的影响，指导撒哈拉以南非洲儿童的抗逆转录病毒治疗建议，并通过评估为接受抗逆转录病毒治疗的儿童重新接种麻疹病毒疫苗的政策，加强消除麻疹战略。

DESCRIPTION (provided by applicant): Understanding the impact of antiretroviral therapy (ART) on pathogen-specific immune reconstitution to endemic infections in children initiating ART in sub-Saharan Africa is critical to the optimal care of HIV-1 - infected children and the effective use of scarce resources. The first long-term objective of this proposal is to characterize the degree of pathogen-specific immune reconstitution in children initiating ART in sub-Saharan Africa, using immune responses to measles virus as a model. The second long-term objective is to apply recent advances in the understanding of immunologic memory to probe the impact of ART in children on memory T- and B-lymphocyte immune responses to measles virus. The third long-term objective is to assess the impact of ART on population immunity to measles virus as a basis for policy decisions regarding measles revaccination of HIV-1-infected children receiving ART in sub-Saharan Africa. Building upon our studies of measles and measles vaccination in HIV-1-infected children in Lusaka, Zambia, we will conduct a prospective, observational cohort study of HIV-1-infected children initiating ART at public clinics in Lusaka, Zambia to address the following specific aims: 1) characterize the magnitude and quality of mmune reconstitution in HIV-1 infected Zambian children initiating ART and determine pathogen-specific immune reconstitution by measuring memory immune responses to measles virus; 2) measure humoral and cellular immune responses to measles virus before and after revaccination of HIV-1-infected Zambian children receiving ART who lack protective antibody titers; 3) use mathematical models to evaluate the importance for measles elimination of a policy to revaccinate HIV-1-infected children receiving ART in regions of high HIV-1 prevalence. Estimates of the proportion of HIV-1-infected children receiving ART who are protected against measles virus both before and after revaccination will be used in a mathematical model to assess the impact of ART on population immunity to measles virus, with and without a policy of revaccination. The public health relevance of this research, linking epidemiologic and immunologic studies, is to guide ART treatment recommendations for children in sub-Saharan Africa by evaluating the impact of ART on immune reconstitution and immunity to vaccine-preventable diseases, and to enhance strategies for measles elimination by evaluating a policy to revaccinate children receiving ART against measles virus.