抗反转录病毒药物疗法(ART)已经被证明为艾滋病病毒(HIV)感染者的救命疗法。理想的治疗策略在不需要每日进行ART的情况下消除或控制病毒,包括使CD4+T细胞对HIV产生抵抗力和提高宿主抗感染免疫力。
艾滋病病毒储存库是根除病毒治愈艾滋病的主要障碍
长期存活的细胞病毒储存库主要是静息CD4+T细胞或记忆CD4+T细胞，在这类细胞中,HIV整合到细胞基因组,以前病毒的方式存在,不被免疫系统识别,抗病毒药物也对其无效。有关科学家认为,HⅣ感染难以根治的主要原因在于长期存活的细胞病毒储存库的存在。在HIV感染者终止ART后,体内的病毒储存库是实现持久的病毒学缓解所面临的巨大障碍,即使其血浆病毒血症已经得到长时间的成功抑制。
视频来源:TED。翻译及字幕：新五
对于病毒储存库的治疗策略主要是在抗病毒治疗的前提下,激活这类细胞,使前病毒表达,以便免疫系统对其识别和杀伤。
更好地了解 HIV储存库的病理生理学特性以及各种干预措施对其存留的影响,对于研发可成功抵抗HIV或长期控制病毒感染的治疗策略是至关重要的。研究人员认为,任何治愈的可能性显然都需要强有力的和持续的努力去更好地了解机体极为神秘的HIV储存库的建立、构成、维护和更新机制。
大脑中的病毒库与HIV相关的神经认知障碍（HAND）相关？ ——Treating viruses in the brain: Perspectives from NeuroAIDS（治疗大脑中的HIV病毒：来自NeuroAIDS的观点，Neuroscience Letters, 2021）
Abstract：
Aggressive use of antiretroviral therapy has led to excellent viral suppression within the systemic circulation. However, despite these advances, HIV reservoirs still persist. The persistence of HIV within the brain can lead to the development of HIV-associated neurocognitive disorders (HAND). Although the causes of the development of neurocognitive disorders is likely multifactorial, the inability of antiretroviral therapy to achieve adequate concentrations within the brain is likely a major contributing factor. Information about antiretroviral drug exposure within the brain is limited. Clinically, drug concentrations within the cerebrospinal fluid (CSF) are used as markers for central nervous system (CNS) drug exposure. However, significant differences exist; CSF concentration is often a poor predictor of drug exposure within the brain. This article reviews the current information regarding antiretroviral exposure within the brain in humans as well as preclinical animals and discusses the impact of co-morbidities on antiretroviral efficacy within the brain. A more thorough understanding of antiretroviral penetration into the brain is an essential component to the development of better therapeutic strategies for neuroAIDS.
积极使用抗逆转录病毒疗法已导致全身循环中极好的病毒抑制。然而，尽管取得了这些进展，但艾滋病毒储存库仍然存在。艾滋病毒在大脑中持续存在会导致与HIV相关的神经认知障碍（HAND）的发展。尽管神经认知障碍发展的原因可能是多因素的，但抗逆转录病毒疗法无法在大脑中达到足够的浓度可能是主要的促成因素。临床上，脑脊液（CSF）中的药物浓度被用作中枢神经系统（CNS）药物暴露的标志物。但是，存在显着差异，脑脊液浓度通常不能很好地预测大脑内的药物暴露。本文回顾了有关人类以及临床前动物脑内抗逆转录病毒暴露的最新信息，并讨论了合并症对脑内抗逆转录病毒疗效的影响。对抗逆转录病毒渗透到大脑更透彻的了解是开发更好的艾滋相关的神经病治疗策略的重要组成部分。Poor antiretroviral brain penetration is likely a contributing factor to neuroAIDS.
Drug concentrations in the CSF is a poor indicator of brain concentrations.
Current knowledge of brain, not CSF, exposure of HIV drugs is reviewed herein.
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1.Nat Immunol.2015 May 19;16(6)584-589
2.Plasmodium infection reduces the volume of the viral reservoir in SIV-infected rhesus macaques receiving antiretroviral therapy.Retrovirology 2014,11:112.DOI: 10.1186/s12977-014-0112-x3..Nicol Melanie R. and McRae MaryPeace. Treating viruses in the brain: Perspectives from NeuroAIDS[J]. Neuroscience Letters, 2021, 748.DOI: 10.1016/J.NEULET.2021.135691鼓励一下，点个“赞+在看”呗！