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）对撒哈拉以南非洲地区开始ART的儿童中地方性感染的病原体特异性免疫重建的影响，对于HIV-1感染儿童的最佳护理和有效利用稀缺资源至关重要。该提案的第一个长期目标是以麻疹病毒免疫反应为模型，描述撒哈拉以南非洲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的最新进展，探讨儿童ART对记忆T和B淋巴细胞对麻疹病毒的免疫应答的影响。第三个长期目标是评估抗逆转录病毒疗法对人群麻疹病毒免疫力的影响，以此作为撒哈拉以南非洲接受抗逆转录病毒疗法的艾滋病毒1型感染儿童麻疹疫苗再接种的政策决定依据。基于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的研究，我们将对赞比亚卢萨卡公共诊所开始抗逆转录病毒治疗的HIV-1感染儿童进行一项前瞻性、观察性队列研究，以实现以下具体目标：1）描述开始ART的HIV-1感染赞比亚儿童中免疫重建的程度和质量，并确定病原体-通过测量对麻疹病毒的记忆免疫应答来进行特异性免疫重建; 2）测量接受抗逆转录病毒疗法的感染HIV-1的赞比亚儿童在重新接种疫苗之前和之后对麻疹病毒的体液和细胞免疫应答，这些儿童缺乏保护性抗体滴度; 3）使用数学模型评估在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。估计接受抗逆转录病毒疗法的儿童在再接种疫苗前后都能免受麻疹病毒感染的比例，将用于一个数学模型，以评估在有和没有再接种疫苗政策的情况下，抗逆转录病毒疗法对人群麻疹病毒免疫力的影响。这项研究的公共卫生相关性将流行病学和免疫学研究联系起来，旨在通过评估ART对免疫重建和疫苗可预防疾病免疫力的影响来指导撒哈拉以南非洲儿童的ART治疗建议，并通过评估为接受ART的儿童重新接种麻疹病毒疫苗的政策来加强消除麻疹的策略。

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.