Immune Reconstitution of HIV-1 Infected Zambian Children Initiating Antiretrovira

描述(由申请人提供)：了解抗逆转录病毒疗法(ART)对在撒哈拉以南非洲启动抗逆转录病毒疗法(ART)的儿童地方性感染的病原体特异性免疫重建的影响，对于最佳护理感染艾滋病毒-1的儿童和有效利用稀缺资源至关重要。这项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启动抗逆转录病毒治疗的儿童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疗法对人群对麻疹病毒免疫的影响，作为撒哈拉以南非洲接受抗逆转录病毒药物治疗的艾滋病毒-1感染儿童重新接种麻疹疫苗的政策决定的基础。在我们对赞比亚卢萨卡HIV-1感染儿童的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启动ART的HIV-1感染儿童进行前瞻性、观察性队列研究，以解决以下具体目标：1)表征HIV-1感染的赞比亚儿童启动ART的免疫重建的规模和质量，并通过测量对麻疹病毒的记忆免疫反应来确定病原体特异性的免疫重建；2)测量接受ART的HIV-1感染的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)使用数学模型评估在艾滋病毒-1高流行地区为接受抗逆转录病毒治疗的艾滋病毒-1感染儿童重新接种疫苗的政策对消除麻疹的重要性。对在复种前后接受抗逆转录病毒治疗的艾滋病毒-1感染儿童的比例的估计将在数学模型中使用，以评估在有和没有复种政策的情况下，抗逆转录病毒治疗对人群对麻疹病毒免疫的影响。这项研究的公共卫生意义在于，将流行病学和免疫学研究联系起来，通过评估抗逆转录病毒疗法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击麻疹病毒抗逆转录病毒药物的儿童重新接种疫苗的政策，加强消除麻疹的战略。

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.