School of Public Health, Anhui Medical University, Hefei, China.
The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
J Immunol. 2024 Jun 1;212(11):1609-1620. doi: 10.4049/jimmunol.2300777.
In individuals diagnosed with AIDS, the primary method of sustained suppression of HIV-1 replication is antiretroviral therapy, which systematically increases CD4+ T cell levels and restores immune function. However, there is still a subset of 10-40% of people living with HIV who not only fail to reach normal CD4+ T cell counts but also experience severe immune dysfunction. These individuals are referred to as immunological nonresponders (INRs). INRs have a higher susceptibility to opportunistic infections and non-AIDS-related illnesses, resulting in increased morbidity and mortality rates. Therefore, it is crucial to gain new insights into the primary mechanisms of immune reconstitution failure to enable early and effective treatment for individuals at risk. This review provides an overview of the dynamics of key lymphocyte subpopulations, the main molecular mechanisms of INRs, clinical diagnosis, and intervention strategies during immune reconstitution failure, primarily from a multiomics perspective.
在被诊断出艾滋病的个体中，持续抑制 HIV-1 复制的主要方法是抗逆转录病毒疗法，它系统地增加 CD4+T 细胞水平并恢复免疫功能。然而，仍有 10-40%的 HIV 感染者亚群不仅未能达到正常的 CD4+T 细胞计数，而且还经历严重的免疫功能障碍。这些个体被称为免疫无应答者（INRs）。INRs 更容易受到机会性感染和非艾滋病相关疾病的影响，导致发病率和死亡率增加。因此，深入了解免疫重建失败的主要机制对于为处于危险中的个体提供早期和有效的治疗至关重要。本综述主要从多组学的角度概述了关键淋巴细胞亚群的动力学、INRs 的主要分子机制、免疫重建失败时的临床诊断和干预策略。
