Eshelman School of Pharmacy, The University of North Carolina, Chapel Hill, North Carolina, USA.
School of Medicine, The University of North Carolina, Chapel Hill, North Carolina, USA.
Clin Pharmacol Ther. 2021 Apr;109(4):918-927. doi: 10.1002/cpt.2186. Epub 2021 Feb 28.
Despite advances in treatment, finding a cure for HIV remains a top priority. Chronic HIV infection is associated with increased risk of comorbidities, such as diabetes and cardiovascular disease. Additionally, people living with HIV must remain adherent to daily antiretroviral therapy, because lapses in medication adherence can lead to viral rebound and disease progression. Viral recrudescence occurs from cellular reservoirs in lymphoid tissues. In particular, lymph nodes are central to the pathology of HIV due to their unique architecture and compartmentalization of immune cells. Understanding how antiretrovirals (ARVs) penetrate lymph nodes may explain why these tissues are maintained as HIV reservoirs, and how they contribute to viral rebound upon treatment interruption. In this report, we review (i) the physiology of the lymph nodes and their function as part of the immune and lymphatic systems, (ii) the pathogenesis and outcomes of HIV infection in lymph nodes, and (iii) ARV concentrations and distribution in lymph nodes, and the relationship between ARVs and HIV in this important reservoir.
尽管在治疗方面取得了进展,但找到治愈 HIV 的方法仍是当务之急。慢性 HIV 感染与合并症的风险增加有关,如糖尿病和心血管疾病。此外,HIV 感染者必须坚持每日接受抗逆转录病毒治疗,因为药物依从性的下降会导致病毒反弹和疾病进展。病毒的复发来自于淋巴组织中的细胞储库。特别是,淋巴结由于其独特的结构和免疫细胞的分区化,是 HIV 病理学的核心。了解抗逆转录病毒药物 (ARV) 如何穿透淋巴结,可以解释为什么这些组织被维持为 HIV 储库,以及它们在治疗中断时如何导致病毒反弹。在本报告中,我们回顾了(i)淋巴结的生理学及其作为免疫和淋巴系统一部分的功能,(ii)HIV 在淋巴结中的发病机制和结果,以及(iii)淋巴结中 ARV 的浓度和分布,以及 ARV 和 HIV 在这个重要储库中的关系。