HIV infection and drug use intersect epidemiologically, and their combination can result in complex effects on brain and behavior. The extent to which drugs affect the health of persons with HIV (PWH) depends on many factors including drug characteristics, use patterns, stage of HIV disease and its treatment, comorbid factors, and age. To consider the range of drug effects, we have selected two that are in common use by PWH: methamphetamine and cannabis. We compare the effects of methamphetamine with those of cannabis, to illustrate how substances may potentiate, worsen, or even buffer the effects of HIV on the CNS. Data from human, animal, and ex vivo studies provide insights into how these drugs have differing effects on the persistent inflammatory state that characterizes HIV infection, including effects on viral replication, immune activation, mitochondrial function, gut permeability, blood brain barrier integrity, glia and neuronal signaling. Moving forward, we consider how these mechanistic insights may inform interventions to improve brain outcomes in PWH.

HIV 感染和吸毒在流行病学上是相互交叉的，它们的结合会对大脑和行为产生复杂的影响。药物对 HIV 感染者 (PWH) 健康的影响程度取决于许多因素，包括药物特性、使用模式、HIV 疾病的阶段及其治疗、合并症因素和年龄。为了考虑药物作用的范围，我们选择了 PWH 常用的两种：甲基苯丙胺和大麻。我们将甲基苯丙胺的作用与大麻的作用进行了比较，以说明物质如何增强、恶化甚至缓冲 HIV 对 CNS 的影响。来自人类、动物和离体研究的数据提供了关于这些药物如何对表征 HIV 感染的持续炎症状态产生不同影响的见解，包括对病毒复制、免疫激活、线粒体功能、肠道通透性、血脑屏障完整性、神经胶质和神经元信号。展望未来，我们考虑这些机械见解如何为干预措施提供信息，以改善 PWH 的大脑结果。