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感染艾滋病毒的药物滥用者的神经心理功能障碍

Neuropsychological Dysfunction among HIV Infected Drug Abusers.

作者信息

Durvasula Ramani S, Hinkin Charles H

机构信息

California State University, Los Angeles.

出版信息

Am J Infect Dis. 2006;2(2):67-73.

Abstract

Human immunodeficiency virus (HIV) has been documented to cause direct and indirect central nervous system dysfunction that can be observed as a progressive decline in neuropsychological functioning in a large proportion of persons with HIV and AIDS. Neuropsychological decline in individuals with HIV is characterized by cognitive and motor slowing, attentional deficits, executive dysfunction and memory impairment (characterized by intact recognition and deficits in learning and delayed recall). Dementia occurs in a relatively small proportion of HIV infected individuals, though milder NP deficits are observed in 30-50% of persons with advanced disease. Recent evidence suggests that drug users, especially stimulant users, are at risk for accelerated progression of their HIV disease, including a greater risk of neuropsychological dysfunction. Methamphetamine may potentiate HIV Tat protein mediated neurotoxicity giving rise to striatal proinflammatory cytokine stimulation and activation of redox-regulated transcription factors. Oxidative stress due to mitochondrial dysfunction is another candidate process underlying the synergistic effects of stimulant use and HIV. Damage to neurotransmitter systems including the dopaminergic, serotonergic and glutamatergic systems which are affected by both stimulant use and HIV is an alternate explanation. Methamphetamine has also been shown to impede the effectiveness of HAART, which could then in turn allow for more rapid HIV disease progression. A greater prevalence of psychiatric disorders, particularly mood, anxiety and substance use disorders are also observed in HIV positive samples relative to the general population. The changing nature of the HIV pandemic is an ongoing challenge to investigators and clinicians working in this field. Emerging issues requiring additional attention are study of the interactive effects of normal aging and HIV on neurocognition as well as study of the effects of co-infection with Hepatitis C.

摘要

人类免疫缺陷病毒(HIV)已被证明会导致直接和间接的中枢神经系统功能障碍,这在很大一部分HIV感染者和艾滋病患者中表现为神经心理功能的逐渐下降。HIV感染者的神经心理衰退表现为认知和运动迟缓、注意力缺陷、执行功能障碍和记忆损害(表现为识别能力正常,但学习和延迟回忆存在缺陷)。痴呆症在相对较少比例的HIV感染者中出现,不过在30%-50%的晚期患者中可观察到较轻的神经心理缺陷。最近的证据表明,吸毒者,尤其是使用兴奋剂的人,其HIV疾病进展加速的风险更高,包括神经心理功能障碍的风险更大。甲基苯丙胺可能会增强HIV Tat蛋白介导的神经毒性,导致纹状体促炎细胞因子的刺激以及氧化还原调节转录因子的激活。线粒体功能障碍导致的氧化应激是兴奋剂使用和HIV协同作用的另一个潜在机制。对包括多巴胺能、5-羟色胺能和谷氨酸能系统在内的神经递质系统的损害是另一种解释,这些系统都会受到兴奋剂使用和HIV的影响。甲基苯丙胺还被证明会阻碍高效抗逆转录病毒治疗(HAART)的有效性,进而可能导致HIV疾病进展更快。相对于普通人群,在HIV阳性样本中还观察到精神障碍,尤其是情绪、焦虑和物质使用障碍的患病率更高。HIV大流行的不断变化性质,对该领域的研究人员和临床医生来说是一个持续的挑战。需要额外关注的新出现问题包括正常衰老和HIV对神经认知的交互作用研究,以及丙型肝炎合并感染的影响研究。

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