Department of Experimental and Clinical Pharmacology, University of Minnesota College of Pharmacy, Minneapolis, MN 55455, USA.
Department of Pharmacotherapy and Outcomes Science, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23298, USA.
Neurosci Lett. 2021 Mar 23;748:135691. doi: 10.1016/j.neulet.2021.135691. Epub 2021 Jan 30.
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.
抗逆转录病毒疗法的积极应用导致全身血液循环中病毒得到了极好的抑制。然而，尽管取得了这些进展，HIV 储库仍然存在。HIV 在大脑中的持续存在可导致 HIV 相关神经认知障碍（HAND）的发生。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一个主要的促成因素。关于大脑中抗逆转录病毒药物暴露的信息有限。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。然而，存在显著差异；CSF 浓度往往是大脑中药物暴露的不良预测指标。本文综述了目前关于人类和临床前动物大脑中抗逆转录病毒暴露的信息，并讨论了合并症对大脑中抗逆转录病毒疗效的影响。更深入地了解抗逆转录病毒进入大脑是开发治疗神经艾滋病更好治疗策略的重要组成部分。
