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

描述(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。心血管疾病和与抗逆转录病毒治疗相关的其他严重并发症的发生率增加，促使人们努力检查治疗中断后病毒的复苏情况。大量研究报告称，大多数接受治疗中断的人都会经历病毒反弹。但最近的研究报道，在急性感染中启动ART的少数受试者在ART停止后实现了对HIV复制的自然控制，但没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。确定导致ART停用后病毒复制的自然控制的关键免疫学因素对于开发成功的免疫治疗干预措施至关重要，以实现在大多数人没有ART的情况下实现病毒复制的自然控制。我们假设ART早期保留了CD8、CD4、抗体记忆和效应器的功能，这将在ART停止后实现有效的病毒控制。这项建议的主要目的是确定早期ART启动时保存的免疫参数，并与ATI后的病毒控制相关。在这笔赠款中，我们将跟踪RV24队列中一组在感染后头两周接受治疗的HI感染患者，这些患者将在至少三年内接受抗逆转录病毒治疗。重要的是，我们将监测这些感染艾滋病毒的受试者在ATI时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，受试者在遗传上不容易控制。通过检查治疗中断前后的这个独特的队列，我们将能够确定保存的记忆T细胞反应和更好的效应器T和B细胞是否与ATI后病毒复制的控制有关。

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.