Nath Avindra, Sacktor Ned
Richard T Johnson Division of Neuroimmunology and Neurological Infections, Department of Neurology, Johns Hopkins University, Baltimore, Maryland, USA.
Curr Opin Neurol. 2006 Aug;19(4):358-61. doi: 10.1097/01.wco.0000236614.51592.ca.
The epidemiology of HIV infection is changing rapidly in the era of highly actively antiretroviral therapy, as the use of such therapy is increasing in all countries. This has had a significant impact on the neurological manifestations of HIV infection, posing new challenges in diagnosis and treatment. This review provides a critical analysis of the recent literature on the impact of highly actively antiretroviral therapy on HIV-related neurological complications and changes in treatment strategies.
It is becoming clear that the brain is an important reservoir for the virus, and neuroinflammatory and neurodegenerative changes may continue despite the adequate use of highly actively antiretroviral therapy. Although this antiretroviral therapy has had a significant impact on the severity of HIV dementia, cognitive impairment persists. With improvement in the immune status following treatment with antiretrovirals, in rare cases the brain can become a target of the immune reconstitution.
Highly actively antiretroviral therapy may need to be optimized in patients with HIV-associated cognitive impairment to achieve maximal central nervous system penetration; however, this therapeutic strategy may not be sufficient for halting the process. In some instances, the antiretroviral drugs themselves may become the problem. New strategies for neuroprotection that also target host genes which control HIV replication are being developed.
在高效抗逆转录病毒治疗时代,随着各国此类治疗的使用不断增加,HIV感染的流行病学正在迅速变化。这对HIV感染的神经表现产生了重大影响,在诊断和治疗方面带来了新的挑战。本综述对近期关于高效抗逆转录病毒治疗对HIV相关神经并发症的影响及治疗策略变化的文献进行了批判性分析。
越来越清楚的是,大脑是病毒的重要储存库,尽管充分使用了高效抗逆转录病毒治疗,神经炎症和神经退行性变化仍可能持续。虽然这种抗逆转录病毒治疗对HIV痴呆的严重程度有重大影响,但认知障碍仍然存在。随着抗逆转录病毒治疗后免疫状态的改善,在罕见情况下,大脑可能成为免疫重建的靶点。
对于有HIV相关认知障碍的患者,可能需要优化高效抗逆转录病毒治疗以实现最大程度的中枢神经系统渗透;然而,这种治疗策略可能不足以阻止该过程。在某些情况下,抗逆转录病毒药物本身可能成为问题。正在开发针对控制HIV复制的宿主基因的神经保护新策略。