Levine Andrew J, Reynolds Sandra, Cox Christopher, Miller Eric N, Sinsheimer Janet S, Becker James T, Martin Eileen, Sacktor Ned
Department of Neurology, National Neurological AIDS Bank, David Geffen School of Medicine, University of California, Los Angeles, CA, USA,
J Neurovirol. 2014 Jun;20(3):243-57. doi: 10.1007/s13365-014-0241-y. Epub 2014 Apr 16.
Both human immunodeficiency virus (HIV)-1 infection and illicit stimulant use can adversely impact neurocognitive functioning, and these effects can be additive. However, significant variability exists such that as-of-yet unidentified exogenous and endogenous factors affect one's risk for neurocognitive impairment. Literature on both HIV and stimulant use indicates that host genetic variants in immunologic and dopamine-related genes are one such factor. In this study, the individual and interactive effects of HIV status, stimulant use, and genotype upon neurocognitive functioning were examined longitudinally over a 10-year period. Nine hundred fifty-two Caucasian HIV+ and HIV- cases from the Multicenter AIDS Cohort Study were included. All cases had at least two comprehensive neurocognitive evaluations between 1985 and 1995. Pre-highly active antiretroviral therapy (HAART) data were examined in order to avoid the confounding effect of variable drug regimens. Linear mixed models were used, with neurocognitive domain scores as the outcome variables. No four-way interactions were found, indicating that HIV and stimulant use do not interact over time to affect neurocognitive functioning as a function of genotype. Multiple three-way interactions were found that involved genotype and HIV status. All immunologically related genes found to interact with HIV status affected neurocognitive functioning in the expected direction; however, only C-C chemokine ligand 2 (CCL2) and CCL3 affected HIV+ individuals specifically. Dopamine-related genetic variants generally affected HIV-negative individuals only. Neurocognitive functioning among HIV+ individuals who also used stimulants was not significantly different from those who did not use stimulants. The findings support the role of immunologically related genetic differences in CCL2 and CCL3 in neurocognitive functioning among HIV+ individuals; however, their impact is minor. Being consistent with findings from another cohort, dopamine (DA)-related genetic differences do not appear to impact the longitudinal neurocognitive functioning of HIV+ individuals.
人类免疫缺陷病毒1型（HIV-1）感染和非法使用兴奋剂都会对神经认知功能产生不利影响，而且这些影响可能会叠加。然而，存在显著的个体差异，以至于尚未明确的外源性和内源性因素会影响一个人发生神经认知障碍的风险。关于HIV和兴奋剂使用的文献表明，免疫和多巴胺相关基因中的宿主基因变异就是这样一个因素。在本研究中，对HIV感染状态、兴奋剂使用和基因型对神经认知功能的个体及交互作用进行了为期10年的纵向研究。研究纳入了多中心艾滋病队列研究中的952名白种人HIV阳性和HIV阴性病例。所有病例在1985年至1995年间至少接受了两次全面的神经认知评估。为避免可变药物方案的混杂效应，对高效抗逆转录病毒治疗（HAART）前的数据进行了检查。使用线性混合模型，将神经认知领域得分作为结果变量。未发现四向交互作用，这表明HIV和兴奋剂使用不会随着时间推移相互作用，以基因型为函数影响神经认知功能。发现了多个涉及基因型和HIV感染状态的三向交互作用。所有被发现与HIV感染状态相互作用的免疫相关基因均按预期方向影响神经认知功能；然而，只有C-C趋化因子配体2（CCL2）和CCL3特异性地影响HIV阳性个体。多巴胺相关基因变异通常仅影响HIV阴性个体。同时使用兴奋剂的HIV阳性个体的神经认知功能与未使用兴奋剂的个体没有显著差异。这些发现支持了CCL2和CCL3中免疫相关基因差异在HIV阳性个体神经认知功能中的作用；然而，它们的影响较小。与另一队列的研究结果一致，多巴胺（DA）相关基因差异似乎不会影响HIV阳性个体的纵向神经认知功能。
