Division of Hematology and.
Crit Rev Clin Lab Sci. 2014 Apr;51(2):98-111. doi: 10.3109/10408363.2013.865702. Epub 2014 Jan 30.
Inflammation and immune activation have been thrust to center stage in the understanding of HIV-1 disease pathogenesis and progression. Early work demonstrated that heightened levels of immune activation correlated with the extent of CD4 + T cell death in lymphoid tissue; however, this concept was not incorporated into the general view of disease pathogenesis. Since these early studies, the extension of life for patients on combination antiretroviral therapies (cART) has heralded a new era of non-AIDS-related diseases and incomplete restoration of immune function. The common link appears to be ongoing inflammation and immune activation. Thus, despite good control of viral loads, persons living with HIV (PLWH) remain at increased risk of inflammatory-associated complications such as cardiovascular disease and certain cancers. HIV-specific mechanisms as well as non-specific generalized responses to infection contribute to ongoing activation of the immune system. An early loss of gastrointestinal (GI) tract mucosal integrity, the pro-inflammatory cytokine milieu, co-infections and marked destruction of lymph node architecture are all factors contributing to the ongoing activation of the immune system as well as impaired immune recovery. It is becoming increasingly evident that the CD4 count and viral load do not provide a complete picture of the underlying state of the immune system. Heightened levels of inflammatory markers have been shown to predict increased mortality and other adverse events. Therefore, it will be important to incorporate these markers into management algorithms as soon as possible. This is particularly relevant in resource-poor countries where difficulties in cART roll-out and access are still encountered and, therefore, a mechanism for prioritizing individuals for therapy would be of value. This review will focus on the closely inter-related concepts of immune activation and inflammation. Both are broad concepts involving the interaction of various key players in the immune system. Importantly, immune activation promotes inflammation and thrombosis and similarly, inflammation and thrombosis induce immune activation. These concepts are thus intricately linked. Studies highlighting the potentially harmful effects of ongoing inflammation/immune activation are reviewed and the contributions of the GI tract "damage" and other co-infections such as CMV are explored. The complications resulting from persistent immune activation include enhanced CD4 + T cell death, lymphoid tissue destruction, and various pathologies related to chronic inflammation. Ultimately, we envision that the long-term management of the disease will incorporate both the identification and the amelioration of the potentially harmful effects of ongoing immune activation and inflammation.
炎症和免疫激活已成为理解 HIV-1 疾病发病机制和进展的核心。早期的研究表明，免疫激活水平的升高与淋巴组织中 CD4+T 细胞死亡的程度相关；然而，这一概念并未被纳入疾病发病机制的一般观点。自这些早期研究以来，接受联合抗逆转录病毒疗法 (cART) 的患者的寿命延长，迎来了非艾滋病相关疾病和免疫功能不完全恢复的新时代。共同的联系似乎是持续的炎症和免疫激活。因此，尽管病毒载量得到了很好的控制，HIV 感染者 (PLWH) 仍面临炎症相关并发症的风险增加，如心血管疾病和某些癌症。HIV 特异性机制以及对感染的非特异性全身性反应导致免疫系统持续激活。胃肠道 (GI) 道粘膜完整性的早期丧失、促炎细胞因子环境、合并感染和淋巴结结构的明显破坏，都是导致免疫系统持续激活和免疫恢复受损的因素。越来越明显的是，CD4 计数和病毒载量并不能提供免疫系统潜在状态的完整画面。炎症标志物水平升高已被证明可预测死亡率增加和其他不良事件。因此，尽快将这些标志物纳入管理算法将非常重要。在资源匮乏的国家，这一点尤为重要，因为在这些国家，cART 的推出和获得仍然存在困难，因此，为治疗确定优先级的机制将具有价值。这篇综述将重点关注免疫激活和炎症这两个密切相关的概念。这两个概念都是广泛的概念，涉及免疫系统中各种关键参与者的相互作用。重要的是，免疫激活促进炎症和血栓形成，同样，炎症和血栓形成也会诱导免疫激活。因此，这些概念是相互关联的。本文综述了强调持续炎症/免疫激活潜在有害影响的研究，并探讨了胃肠道“损伤”和其他合并感染（如 CMV）的作用。持续免疫激活引起的并发症包括增强 CD4+T 细胞死亡、淋巴组织破坏以及与慢性炎症相关的各种病理。最终，我们设想，疾病的长期管理将包括识别和缓解持续免疫激活和炎症的潜在有害影响。
