Markers of Long-Term Suppression of HIV in Pre-adolescents treated from Infancy

描述(申请人提供)：在接受早期治疗的儿童中，HAART导致一种独特的病毒持续状态，即艾滋病毒复制仅由艾滋病毒特异性免疫力较低的抗逆转录病毒药物控制(精英治疗应答者)。我们假设，对婴儿进行长期有效的治疗可能会促进一种不同于长期治疗的成人的HIV持续状态，这种状态包括可以忽略不计的前病毒DNA水平、不可检测到的静止CD4+T细胞潜伏复制能力病毒库、无残留病毒血症、HIV特异性免疫反应、免疫激活和炎症。在PHACS/AMP研究的背景下，我们将在一组青春期前儿童长期精英治疗应答者中衡量下列指标：1)确定早期HAART对围生期感染艾滋病毒的前期青少年和从小接受治疗的青少年中艾滋病毒前病毒和复制能力的储备库大小的长期影响；2)检测从婴儿期开始接受HAART对围产期艾滋病毒感染前期和青少年中艾滋病毒持久性和免疫结局的长期影响；以及3)确定早期HAART对从小接受治疗的围产期艾滋病毒感染前期和青少年中艾滋病毒前病毒和复制能力的多样性的长期影响。拟议的项目将提高关于早期HAART对现在可能活到成年的婴儿的长期病毒学和免疫学影响的科学知识，并为在旨在实现儿童和青少年艾滋病毒治愈的临床试验中确定艾滋病毒治愈提供一个关键框架。

DESCRIPTION (provided by applicant): In early-treated children, HAART leads to a unique state of viral persistence whereby HIV replication is controlled solely by antiretroviral drugs wit little HIV-specific immunity (elite-treatment responders). We hypothesize that long-term early effective therapy of infants may promote a state of HIV persistence that is distinct from long-term treated adults that is comprised of negligible levels of proviral DNA, a nondetectable resting CD4+T cell latent replication-competent viral reservoir, absent residual viremia, HIV specific immune responses, immune activation and inflammation. In the context of the PHACS/AMP study, we will measure the following in a cohort of preadolescent pediatric long-term elite treatment responders: 1) Determine the long- term effects of early HAART on the size of proviral and replication-competent HIV reservoirs in perinatally HIV- infected pre-adolescents and adolescents treated from infancy, 2) Examine the long-term effects of early HAART from infancy on the dynamics of HIV persistence and immune outcomes in perinatally HIV-infected pre-adolescents and adolescents, and 3) Determine the long-term effect of early HAART on diversity of proviral and replication-competent HIV reservoirs in pre-adolescents and adolescents treated from infancy. The proposed project will improve scientific knowledge on the long-term virologic and immunologic effects of early HAART for infants who are now likely to survive to young adulthood and provide a critical framework for defining HIV CURE in clinical trials aimed at achieving HIV CURE for children and adolescents.