HIV Subtype D Is Associated with Dementia, Compared with Subtype A, in Immunosuppressed Individuals at Risk of Cognitive Impairment in Kampala, Uganda
HIV Subtype D Is Associated with Dementia, Compared with Subtype A, in Immunosuppressed Individuals at Risk of Cognitive Impairment in Kampala, Uganda
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DOI：
10.1086/605284
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发表时间：
2009-09-01
影响因子：
11.8
通讯作者：
Quinn, Thomas C.
中科院分区：
文献类型：
--
作者：
Sacktor, Ned;Nakasujja, Noeline;Quinn, Thomas C.
背景在美国，进化枝B是主要的人类免疫缺陷病毒（HIV）亚型，而在撒哈拉以南非洲，进化枝A、C和D是主要的亚型。HIV亚型可能对HIV疾病进展有影响。据我们所知，艾滋病毒亚型对痴呆症风险的影响尚未得到研究。本研究的目的是探讨艾滋病毒亚型和艾滋病毒相关的认知功能障碍的严重程度之间的关系，在乌干达开始抗逆转录病毒治疗的个人。60名未接受过抗逆转录病毒治疗的HIV感染者，有晚期免疫抑制，有HIV相关认知功能障碍的风险，接受了神经学、神经心理学和功能评估，并对gag和gp 41区域进行了亚型分析。使用gag和gp 41区域的一部分通过序列分析产生亚型分配。33例HIV感染者感染A亚型，2例感染C亚型，9例感染D亚型，16例感染A/D重组体。9例D亚型HIV感染者中有8例（89%）患有痴呆，而33例A亚型HIV感染者中有7例（24%）患有痴呆（P = 0.004）。这些结果表明，在未经治疗的HIV感染者中，晚期免疫抑制有发展HIV相关认知障碍的风险，HIV痴呆在感染D亚型病毒的患者中可能比感染A亚型病毒的患者更常见。据我们所知，这些发现提供了第一个证据，证明艾滋病毒亚型可能具有导致认知障碍的能力的致病因素。需要进一步的研究来证实这一观察结果，并确定D亚型导致神经发病风险增加的机制。
Background. In the United States, clade B is the predominant human immunodeficiency virus (HIV) subtype, whereas in sub-Saharan Africa, clades A, C, and D are the predominant subtypes. HIV subtype may have an impact on HIV disease progression. The effect of HIV subtype on the risk of dementia has, to our knowledge, not been examined. The objective of this study was to examine the relationship between HIV subtype and the severity of HIV-associated cognitive impairment among individuals initiating antiretroviral therapy in Uganda.Methods. Sixty antiretroviral-naive HIV-infected individuals with advanced immunosuppression who were at risk of HIV-associated cognitive impairment underwent neurological, neuropsychological, and functional assessments, and gag and gp41 regions were subtyped. Subtype assignments were generated by sequence analysis using a portion of the gag and gp41 regions.Results. Thirty-three HIV-infected individuals were infected with subtype A, 2 with subtype C, 9 with subtype D, and 16 with A/D recombinants. Eight (89%) of 9 HIV-infected individuals with subtype D had dementia, compared with 7 (24%) of 33 HIV-infected individuals with subtype A (P = .004).Conclusions. These results suggest that, in untreated HIV-infected individuals with advanced immunosuppression who are at risk of developing HIV-associated cognitive impairment, HIV dementia may be more common among patients infected with subtype D virus than among those infected with subtype A virus. These findings provide the first evidence, to our knowledge, to demonstrate that HIV subtypes may have a pathogenetic factor with respect to their capacity to cause cognitive impairment. Additional studies are needed to confirm this observation and to define the mechanism by which subtype D leads to an increased risk of neuropathogenesis.