大脑是艾滋病病毒持续/潜伏感染的重要储库之一，常导致艾滋病相关神经认知障碍（HAND）。然而，大脑中艾滋病病毒的动态是一个研究不足的领域，对于HAND的发展和进展机制知之甚少。这个问题主要是由于缺乏可复制人类大脑细胞和分子复杂性的适宜体外模型所致。因此，迫切需要这样的模型来研究艾滋病神经病理生理学以及为HAND开发治疗方法。由诱导多能干细胞（iPSCs）生产的三维（3D）脑器官样体现在提供了一种临床相关的体外模型，用于研究艾滋病病毒在大脑中的感染和病理生理机制。最近，有大量的出版物表明该模型对神经生物学和脑部疾病以及艾滋病感染的研究具有可行性和优势。在此，我们描述了iPSC衍生的含有人类微胶质细胞的脑器官样体的发展，包括优势/挑战，并着重介绍其用于模拟艾滋病病毒在大脑中的感染的适用性。版权所有©2023 Elsevier Inc.

The brain is one of the important reservoir sites for HIV persistent/latent infection that often leads to HIV-associated neurocognitive disorders (HAND). However, HIV dynamics in the brain is an understudied area and little is known about mechanisms underlying the development and progression of HAND. This issue is mainly due to the lack of suitable in vitro models that can recapitulate the cellular and molecular complexity of the human brain. Hence, there is an urgent need for such models to study HIV neuropathogenesis and to develop therapeutics for HAND. The emergence of three-dimensional (3D) brain organoids generated from induced pluripotent stem cells (iPSCs) has now provided a clinically relevant in vitro model to study HIV brain infection and neuropathogenesis. Recently, there have been a noticeable number of publications that demonstrate the feasibility and advantages of this model for studies of neurobiology and brain disorders as well as HIV infection. Here, we describe the development of iPSC-derived human microglia-containing brain organoids, including advantages/challenges, and focus on their applicability for modeling HIV brain infection.Copyright © 2023. Published by Elsevier Inc.