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有两篇论文指出鸡尾酒疗法可减少60%~80%的死亡:“A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic millimeter or less,” New England Journal of Medicine 337(1997),and “Treatment with indinavir,zidovudine,and lamivudine in adults with human immunodeficiency virus infection and prior antiretroviral therapy,” New England Journal of Medicine 337(1997).
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9 但是,医生,我不觉得自己生病了
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圣克莱医院中HIV阳性患者的相关描述,来自笔者的观察。
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关于哪个时间点进行抗病毒治疗才正确的争辩,详见:“When to start antiretroviral therapy—ready when you are?” New England Journal of Medicine 360(2009).
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HIV的感染起始为一种单一的“创始病毒”所引发,此发现震惊了整个医学界。部分人士相信此创始病毒的特性,将导向新型疫苗的开发。此事首度刊载于:“Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection,” Proceedings of the National Academy of Sciences 105(2008).
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T细胞如何被HIV感染,并通过何种机制遭到破坏,详见:“HIV preferentially infects HIV-specific CD4+ T cells,” Nature 417(2002).
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大部分HIV在肠道中进行复制,详见:“Getting to the guts of HIV pathogenesis,” Journal of Experimental Medicine 200(2004).
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大量研究都已在肠道及其他黏膜组织中检测出淋巴细胞的密集网络,例如:“Overview of the mucosal immune system,” Current Topics in Microbiology and Immunology 146(1989).
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关于黏膜中的淋巴细胞在H IV感染上的重要性的讨论,详见:“HIV pathogenesis:the first cut is the deepest,” Nature Immunology 6(2005).
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让人惊讶的是,不管是通过黏膜路径(直肠或阴道)感染,还是通过静脉,其细胞的减少趋势相同。详见:“Gastrointestinal tract as a major site of CD4+ T cell depletion and viral replication in SIV infection,” Science 280(1998).
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许多论文已指出感染后,肠道内的T淋巴细胞的破坏。早期发表的其中一篇:“Severe CD4+ T-cell depletion in gut lymphoid tissue during primary human immunodeficiency virus type 1 infection and substantial delay in restoration following highly active antiretroviral therapy,” Journal of Virology 77(2003).
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首篇探讨CCR5在病毒进入人体上的重要性,详见:“Identification of a major co-receptor for primary isolates of HIV-1,” Nature 381(1996).
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HIV的包膜蛋白如何与人体细胞进行融合,详见:“The HIV Env-mediated fusion reaction,” Biomembranes 1614(2003).
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每个人血液中的细胞数量变化相当大,计算其变化范围才会使数据有意义。此变化的平均数主要关乎性别和年龄,详见:“Laboratory control values for CD4 and CD8 T lymphocytes:implications for HIV-1 diagnosis,” Clinical Experimental Immunology 88(1992).
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HIV每天约能复制出100亿个单体,详见:“HIV-1 dynamics in vivo:Virion Clearance Rate,Infected Cell Life-Span,and Viral Generation Time,” Science 271(1996).
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HIV可通过直接或间接机制,引发细胞的大量死亡。关于细胞死亡的机制,详见:Cell Death during HIV Infection ,edited by Andrew D. Badley(CRC Press,2006).
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停止抗病毒疗程将导致病毒的突变与抗药性的产生,详见:“Basic science kinetics of HIV-1 RNA and resistance-associated mutations after cessation of antiretroviral combination therapy,” AIDS 15(2001).
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10 Delta32突变
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首篇探讨由于缺乏CCR5因而对HIV的感染产生抵抗性的论文:“Homozygous defect in HIV-1 co-receptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection,” Cell 86(1996).
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大部分具有Delta32(Δ32)的个体仍能过着健康的生活,但有少数研究指出缺乏CCR5基因的个体为感染西尼罗病毒的高风险群体。这些研究结果彼此并不一致。我们尚无法确定CCR5的缺失将引发的各种结果。其余研究则指出,Delta32突变对于部分疾病可提供保护,例如脑型疟疾等。各方面研究可参见:“CCR5 deficiency increases risk of symptomatic West Nile virus infection,” Journal of Experimental Medicine 203(2006);“CCR5 deficiency is a risk factor for early clinical manifestations of West Nile virus infection but not for viral transmission,” Journal of Infectious Diseases 201(2010);“Role of chemokines polymorphisms in diseases,” Immunology Letters 145(2012).
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绝大多数感染性病毒都会通过CCR5受体进入细胞,详见何大一的论文:“Genotypic and phenotypic characterization of HIV-1 patients with primary infection,” Science 261(1993).
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不论是通过性行为,还是静脉注射,或母体至胎儿等途径,病毒都是通过CCR5进行传染的:“Macrophage-tropic variants initiate human immunodeficiency virus type 1 infection after sexual,parenteral,and vertical transmission,” Journal of Clinical Investigation 94(1994).
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CCR5的Delta32突变,在西欧人中相当常见,相关报告参见:“Resistance to HIV-1 infection in Caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene,” Nature 382(1996);“The geographic spread of the CCR5 Delta32 HIV-resistance allele,” PLoS Biology 3(2005).
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许特尔在医学院图书馆中所读到的,同时也是第一篇描述Delta32突变与HIV之关联的论文:“Resistance to HIV-1 infection in Caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene,” Nature 6593(1996).
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11 呼叫所有非凡控制者
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