Viral dynamics of rebound and control following early treatment of HIV/SIV

摘要 ART后能够持久控制艾滋病毒反弹的精选患者的惊人鉴定 在ANRS Visconi队列中的终止，或在密西西比州婴儿等案例中，突出了 艾滋病毒持续缓解的可能性，并提供了艾滋病毒缓解可能是 在临床上是可以实现的。在其中几种情况下，后处理控制的特点是非常低，但 可检测到的艾滋病毒感染细胞的存在意味着至少在一些病毒缓解的情况下，平衡可能 在HIV-1和宿主之间发生了冲突。 病毒持续缓解或最终反弹的机制(S)， 艺术上的中断是不被理解的。此外，没有经过验证的生物标记物可以预测 治疗中断期间的临床结果。因此，详细了解这些因素 在缺乏抗逆转录病毒治疗的情况下，指示艾滋病毒抑制或复发对于开发治疗方法至关重要 在接受抗逆转录病毒治疗的患者中，通过治疗促进艾滋病毒-1的缓解。 因此，我们建议进行详细的研究，以确定早期抗逆转录病毒治疗对病毒学和 与实现艾滋病毒缓解和持久病毒控制相关的免疫学结果 艺术的停止。这些研究包括多学科合作，以具有最大的广度 调查，并最终产生最大的科学影响。我们建议的调查包括分析 对感染艾滋病毒的成人和儿童患者进行的研究。我们亦会在非政府机构进行平行研究 人类灵长类，包括新的根除疗法的临床前评估。

ABSTRACT The striking identification of select patients who were able to durably control HIV rebound after ART discontinuation in the ANRS Visconti cohort, or in cases such as the Mississippi baby, have highlighted the possibility of sustained HIV remission and provided the first proof of concept that HIV remission may be clinically achievable. In several of these cases, post-treatment control is characterized by the very low, but detectable presence of HIV infected cells implying that in at least some cases of viral remission, a balance may have been struck between HIV-1 and the host. The mechanism(s) by which these reservoirs are subject to sustained virologic remission or ultimately rebound, upon ART interruption is not understood. Moreover, there is no validated biomarker that can predict clinical outcome during a treatment interruption. Therefore, a detailed understanding of the factors that dictate HIV suppression or relapse, in the absence of antiretroviral therapy, is critical to develop approaches to therapeutically foster HIV-1 remission in ART-treated patients. Thus, we propose detailed studies to define the impact of early antiretroviral therapy on virologic and immunologic outcomes that are relevant to achieving HIV remission and durable virus control after the cessation of ART. These studies encompass multi-disciplinary collaborations, to have the greatest breadth of investigation, and ultimately the greatest scientific impact. Our proposed investigations include analytic studies in both HIV-infected adult and pediatric patients. We will also conduct parallel studies in non- human primates, including the pre-clinical evaluation of novel eradication therapeutics.