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: 8992892
• 负责人: Lydie Trautmann
• 金额: $ 69.24万
• 依托单位: HENRY M. JACKSON FDN FOR THE ADV MIL/MED
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-06-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8992892
• 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; Genetic Predisposition to Disease; Grant; Gut associated lymphoid tissue; HIV; HIV Infections; Health; Immune; Immune response; Immunity; Immunologic Factors; Immunotherapeutic agent; Incidence; Individual; Infection; Inflammation; Interruption; Intervention; Lead; Literature; Measures; Mediating; Memory; Modeling; Monitor; PHEMX gene; Participant; Plasma; Reporting; Staging; Survival Analysis; T cell response; T memory cell; T-Cell Depletion; T-Lymphocyte; Therapeutic Intervention; Viral; Viremia; Virus Replication; Withdrawal; Withholding Treatment; adaptive immunity; antiretroviral therapy; base; cell killing; cohort; experience; novel; 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艾滋病毒感染者的长期解决方案。心血管疾病和其他与抗逆转录病毒治疗相关的严重并发症的发病率增加，促使人们努力检查在治疗中断后病毒的死灰复燃。大量研究报告说，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抗逆转录病毒治疗的受试者在停止抗逆转录病毒治疗后实现了对HIV复制的自然控制，而不具有精英控制者的遗传特征，这为分析治疗中断（ATI）后病毒复制的自然控制提供了概念证明。确定在抗逆转录病毒药物停药后对病毒复制进行自然控制的关键免疫因素，对于开发成功的免疫治疗干预措施，使大多数人在没有抗逆转录病毒药物的情况下对病毒复制进行自然控制至关重要。我们假设早期抗逆转录病毒治疗保留了功能性CD8、CD4和抗体记忆以及效应反应，这将在停止抗逆转录病毒治疗后实现有效的病毒控制。本建议的主要目的是确定早期抗逆转录病毒治疗时保存的免疫参数，以及ATI后与病毒控制相关的免疫参数。在这项拨款中，我们将跟踪一组来自RV24队列的hi感染受试者，这些受试者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，我们将监测这些艾滋病毒感染者在ATI上控制病毒血症的能力。RV254队列为研究与病毒控制相关的最佳免疫反应提供了最佳环境，这些受试者在遗传上不容易控制病毒。通过在治疗中断前后检查这个独特的队列，我们将能够确定保留的记忆T细胞反应和更好的效应T细胞和B细胞是否与ATI后病毒复制的控制有关。