Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China; Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China.
Clinical and Research Center of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
Int J Infect Dis. 2019 Sep;86:178-187. doi: 10.1016/j.ijid.2019.07.037. Epub 2019 Aug 6.
Most previous studies on poor immunological responders (PIRs) have been performed on one cohort at one time-point following highly active antiretroviral therapy (HAART). The aim of this study was to investigate whether there are different subtypes of PIR and whether a certain population might achieve better immune reconstitution following longer HAART.
This study was designed as an ambispective cohort study, including a 4-5-year retrospective study and a 2-year prospective follow-up investigation. Thymic output, activated T cell and regulatory T cell (Treg) subset frequencies, expression levels of interferon-stimulated genes, and plasma concentrations of neopterin were determined at 4-5 years and 6-7 years following HAART initiation.
PIRs were subdivided into two populations after 4-5 years of HAART, according to the kinetics of T cell recovery. Type II PIRs exhibited a significantly lower percentage of naïve CD4 T cells and CD31 naïve CD4 T cells compared with type I PIRs. After an additional 2 years of HAART treatment, type I PIRs showed a better outcome than type II PIRs. Furthermore, it was found that 2 years of additional HAART could persistently improve thymic output.
The two PIR subgroups are different in terms of immune characteristics and the response to prolonged HAART.
大多数关于免疫应答不良者（PIR）的既往研究均是在高效抗逆转录病毒治疗（HAART）后某一时间点对单一队列进行的。本研究旨在探究是否存在不同类型的 PIR，以及特定人群是否可能在接受更长时间的 HAART 后获得更好的免疫重建。
本研究设计为前瞻性队列研究，包括 4-5 年的回顾性研究和 2 年的前瞻性随访调查。在 HAART 开始后 4-5 年和 6-7 年时，测定了胸腺输出、活化 T 细胞和调节性 T 细胞（Treg）亚群频率、干扰素刺激基因的表达水平以及新蝶呤的血浆浓度。
根据 T 细胞恢复的动力学，在 HAART 治疗 4-5 年后将 PIR 分为两群。与 I 型 PIR 相比，II 型 PIR 表现出明显更低的幼稚 CD4 T 细胞和 CD31 幼稚 CD4 T 细胞百分比。在接受额外 2 年的 HAART 治疗后，I 型 PIR 比 II 型 PIR 表现出更好的结果。此外，还发现 2 年的额外 HAART 可持续改善胸腺输出。
这两个 PIR 亚组在免疫特征和对延长 HAART 的反应方面存在差异。
