Immunologic and virologic evolution during periods of intermittent and persistent low-level viremia
Immunologic and virologic evolution during periods of intermittent and persistent low-level viremia
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DOI：
10.1097/00002030-200404300-00005
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发表时间：
2004-04-30
期刊：
影响因子：
3.8
通讯作者：
Deeks, SG
中科院分区：
文献类型：
--
作者：
Karlsson, AC;Younger, SR;Deeks, SG
背景：HIV复制、HIV特异性T细胞应答和T细胞活化均对未经治疗的HIV感染的疾病结局有贡献。这些因素的相互作用还没有得到很好的理解，特别是在设置抗逆转录病毒therapy.Methods：这是一个纵向研究的抗逆转录病毒治疗的患者血浆HIV RNA水平< 1000拷贝/毫升。患者被分为三组：抑制性病毒血症、间歇性病毒血症（“暂时性”）和持续性低水平病毒血症。使用干扰素-γ ELISPOT测量HIV特异性免疫。T细胞活化通过CD 38和HLA-DR共表达来定义。使用表型敏感性assay.Results：HIV特异性CD 8 T细胞反应的广度和幅度是更大的间歇性或持续性病毒血症患者相比，抑制病毒血症的患者。相反，T细胞活化仅在持续病毒血症患者中显著升高。持续性低水平病毒血症的患者具有中等水平的表型抗逆转录病毒药物耐药性，并随时间推移而增加。病毒学失败（确认病毒载量增加> 1000 HIV RNA拷贝/ml）主要观察到在持续viremic group.Conclusions：抗逆转录病毒治疗的个体间歇性病毒血症出现安装一个有效的HIV特异性T细胞反应，而没有经历免疫激活水平的增加。这可能会限制病毒的进化和耐药性的出现。相反，持续低水平病毒血症的抗逆转录病毒治疗个体表现出整体免疫激活的显著增加和随后治疗失败的显著风险。较高的病毒血症和较强的免疫激活可能协同作用，加速全身耐药性的发展。(C)2004年利平科特威廉姆斯威尔金斯。
Background: HIV replication, HIV-specific T-cell responses and T-cell activation each contributes to disease outcome during untreated HIV infection. The interaction of these factors is not well understood, particularly in the setting of antiretroviral therapy.Methods: This is a longitudinal study of antiretroviral-treated patients with plasma HIV RNA levels < 1000 copies/ml. Patients were divided into three groups: suppressed viremia, intermittent viremia ('blips') and persistent low-level viremia. HIV-specific immunity was measured using interferon-gamma ELISPOT. T-cell activation was defined by CD38 and HLA-DR co-expression. Drug resistance was quantified using a phenotypic susceptibility assay.Results: The breadth and the magnitude of the HIV-specific CD8 T-cell response was greater in patients with either intermittent or persistent viremia compared to patients with suppressed viremia. In contrast, T-cell activation was significantly elevated only in those patients with persistent viremia. Patients with persistent low-level viremia had moderate levels of phenotypic antiretroviral drug resistance that increased over time. Virologic failure (confirmed increase in viral load > 1000 HIV RNA copies/ml) was primarily observed in the persistently viremic group.Conclusions: Antiretroviral-treated individuals with intermittent viremia appear to mount an effective HIV-specific T-cell response while not experiencing increases in the level of immune activation. This may limit viral evolution and emergence of drug resistance. In contrast, antiretroviral-treated individuals with persistent low-level viremia exhibit significant increases in overall immune activation and a substantial risk of subsequent treatment failure. It is likely that higher viremia and stronger immune activation act synergistically to accelerate the development of systemic drug resistance. (C) 2004 Lippincott Williams Wilkins.