Natural Killer Cells as Effectors in HIV Cure Strategies

抗逆转录病毒疗法（ART）已导致艾滋病毒感染者的预期寿命不再明显低于未感染者。然而，ART必须每天服用，有副作用，并伴随着巨大的经济成本。这再次强调了艾滋病毒的治疗。治愈的障碍是一群被称为水库的感染细胞，它们对治疗和免疫系统都是不可见的。最近的研究表明，在艾滋病毒感染过程中早期接受治疗的患者具有较低的病毒库，有些患者在长期停止ART后可以控制病毒复制。这被称为“治疗后控制”（PTC），是HIV感染缓解的一种形式。如果我们了解它，PTC可能会帮助我们找到治愈艾滋病毒的方法。到目前为止，我们还不能预测哪些患者会成为治疗后控制者。一些数据表明，一种称为自然杀伤（或“NK”）细胞的免疫细胞可能在这种现象中发挥重要作用。在这项研究中，我们将使用两个大型队列的艾滋病毒感染者，他们在感染早期开始ART（称为SPARTAC和石楠），以确定NK细胞的特征是否会影响储库大小，如何预测将在治疗结束后控制病毒复制的患者，并找出早期ART如何影响NK细胞功能。如果我们能发现NK细胞如何帮助诱导病毒的控制，这样治疗就可以停止一段时间，这将有助于我们在寻找治愈HIV感染的方法时计划新的治疗方法。

Antiretroviral therapy (ART) has resulted in the life expectancy of HIV infected individuals no longer being significantly less than uninfected people. However, ART must be taken daily, has side effects and comes with significant financial costs. This has placed renewed emphasis on curing HIV. The barrier to a cure is a population of infected cells termed the reservoir, that remain invisible to both therapy and the immune system. Recent studies have shown that patients treated early in the course of HIV infection have lower viral reservoirs, and some can control viral replication after stopping ART for long periods of time. This is termed 'post treatment control' (PTC), and is a form of remission from HIV infection. If we understand it, PTC may help us find a cure for HIV. As of yet, we cannot predict which patients will and will not become post-treatment controllers. Some data suggests that a type of immune cell - called a Natural Killer (or 'NK') cell - might play an important role in this phenomenon.In this study, we will use two large cohorts of HIV infected patients who started ART early in infection (called SPARTAC and HEATHER) to determine if characteristics of NK cells can affect reservoir size, how to predict patients who will control viral replication off therapy, and find out how early ART will affect NK cell function. If we can find out how NK cells may help induce control of the virus, such that treatment can be stopped for a while, this will help us plan new treatments as we search for a cure for HIV infection.