Preservation of adaptive immunity leads to HIV control upon treatment cessation.

保留适应性免疫可以在停止治疗后控制艾滋病毒。

• 批准号: 8659596
• 负责人: Lydie Trautmann
• 金额: $ 85.9万
• 依托单位: VGTI FLORIDA
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8659596
• 关键词: Acute; Address; Adverse effects; Aftercare; Anti-Retroviral Agents; Antibodies; Avidity; B-Lymphocytes; Biological Preservation; CD4 Positive T Lymphocytes; CD4/CD8 ratio procedure; CD8B1 gene; Cardiovascular Diseases; Cell physiology; Characteristics; Chronic; Data; Development; Early treatment; Exhibits; Frequencies; Generations; Genetic; Grant; Gut associated lymphoid tissue; HIV; HIV Infections; Immune; Immune response; Immunity; Immunologic Factors; Immunotherapeutic agent; Incidence; Individual; Infection; Inflammation; Interruption; Intervention; Lead; Literature; Measures; Mediating; Memory; Modeling; Monitor; Participant; Plasma; Reporting; Solutions; Staging; Survival Analysis; T cell response; T memory cell; T-Cell Depletion; T-Lymphocyte; Therapeutic Intervention; Viral; Viremia; Withdrawal; Withholding Treatment; adaptive immunity; antiretroviral therapy; base; cell killing; cohort; experience; novel; public health relevance; reconstitution; response; success

DESCRIPTION (provided by applicant): It is becoming increasingly evident that antiretroviral treatment is not a long-term solution for HIV- infected subjects. The increased incidence of cardiovascular diseases and other serious complications associated with ART have prompted the efforts to examine viral resurgence upon treatment interruption. Large numbers of studies have reported that the majority of people who undergo treatment interruption would experience viral rebound. But recent studies reported that a small number of subjects that initiated ART in acute infection achieved natural control of HIV replication after ART cessation without having the genetic characteristics of elite controllers, providing the proof of concept for a natural contol of viral replication after analytical treatment interruption (ATI). Identifying key immunological factors responsible for this natural control of viral replication after ART withdrawal is crucial fr the development of successful immunotherapeutic interventions to achieve a status that would allow natural control of viral replication in the absence of ART in most individuals. We hypothesize that very early ART preserves functional CD8, CD4 and antibody memory and effector responses and this will enable efficient viral control upon cessation of ART. The major objective of this proposal is to identify immune parameters preserved by very early ART initiation and associated with viral control after ATI. In this grant, we will follow a group of HI-infected subjects from the RV24 cohort treated in the first two weeks of infection and that will remain under ART for at least three years. Importantly, we will monitor these same HIV-infected subjects for their ability to control viremia upon ATI. The RV254 cohort provides the best setting to study optimal immune responses associated with viral control in subjects that are not genetically predisposed to control. By examining this unique cohort before and after treatment interruption, we will be able determine whether preserved memory T cell responses and better effector T and B cells are associated with control of viral replication after ATI.

描述（由申请人提供）：越来越明显的是，抗逆转录病毒治疗不是HIV感染受试者的长期解决方案。与ART相关的心血管疾病和其他严重并发症的发病率增加促使人们努力检查治疗中断后的病毒复活。大量的研究报告说，大多数接受治疗中断的人会经历病毒反弹。但最近的研究报道，少数在急性感染中开始ART的受试者在ART停止后实现了HIV复制的自然控制，而不具有精英控制者的遗传特征，这为分析性治疗中断（ATI）后病毒复制的自然控制提供了概念证明。确定负责ART停药后病毒复制的这种自然控制的关键免疫因素对于成功的免疫干预措施的发展至关重要，以实现在大多数个体中不存在ART的情况下允许病毒复制自然控制的状态。我们假设，非常早期的ART保留功能的CD8，CD4和抗体的记忆和效应器的反应，这将使有效的病毒控制后停止的ART。这项建议的主要目的是确定保留非常早期的ART启动和相关的ATI后病毒控制的免疫参数。在这项资助中，我们将跟踪一组来自RV 24队列的HI感染受试者，他们在感染的前两周接受治疗，并将继续接受ART治疗至少三年。重要的是，我们将监测这些相同的HIV感染受试者在ATI时控制病毒血症的能力。RV254队列提供了研究与在遗传上不倾向于控制的受试者中的病毒控制相关的最佳免疫应答的最佳设置。通过在治疗中断之前和之后检查这个独特的队列，我们将能够确定保存的记忆T细胞应答和更好的效应T和B细胞是否与ATI后病毒复制的控制相关。