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γδ T Cell Subpopulations Associate with Recovery of Memory Function in Indonesian HIV Patients Starting Antiretroviral Therapy
AIDS Research and Human Retroviruses ( IF 1.5 ) Pub Date : 2022-09-12 , DOI: 10.1089/aid.2021.0171
Ibnu A Ariyanto 1, 2 , Riwanti Estiasari 3, 4 , Silvia Lee 5, 6 , Patricia Price 2, 6
Affiliation  

Cognitive impairment may persist in HIV patients despite effective antiretroviral therapy (ART). However, recovery is influenced by the neurocognitive domain tested, the severity of HIV disease, and by education. In young adult patients commencing ART in Jakarta, Indonesia, we described improvements in all cognitive domains except memory after 6–12 months on ART. In this study, we address relationships between cytomegalovirus (CMV), γδ T cell profiles and neurocognitive assessments with a focus on memory. The JakCCANDO (Jakarta CMV Cardiovascular ART Neurology Dentistry Ophthalmology) project recruited patients (aged 18–48 years) beginning ART with <200 CD4+ T cells/μL. Cognitive assessments used validated tests of five domains. Flow cytometry was used to assess proportions of Vδ2 and Vδ2+ γδ T cells, and their activation (HLA-DR) and terminal differentiation (CD27/CD45RA+). All patients carried high levels of antibodies reactive with CMV, so the detection of CMV DNA before ART was used to stratify participants into subgroups with a moderate/high or an extremely high burden of CMV. Patients had higher proportions of Vδ2 γδ T cells and fewer Vδ2+ γδ T cells than healthy controls before ART and at 6 months. Z-scores for memory function correlated with proportions of Vδ2+ γδ T cells at both time points. Linear regression analyses confirmed this association. When the detection of CMV DNA was used to stratify the cohort, the association between memory Z-scores and Vδ2+ γδ T cells or CMV antibodies was only discernible in patients with a lower CMV burden. Hence, CMV and Vδ2+ γδ T cells warrant further consideration as factors that may contribute to the poor recovery of memory on ART.

中文翻译:

γδ T 细胞亚群与开始抗逆转录病毒治疗的印度尼西亚 HIV 患者的记忆功能恢复相关

尽管进行了有效的抗逆转录病毒疗法 (ART),认知障碍仍可能在 HIV 患者中持续存在。然而,恢复受测试的神经认知领域、HIV 疾病的严重程度和教育的影响。在印度尼西亚雅加达开始抗逆转录病毒治疗的年轻成年患者中,我们描述了在接受抗逆转录病毒治疗 6-12 个月后除记忆外所有认知领域的改善。在这项研究中,我们解决了巨细胞病毒 (CMV)、γδ T 细胞概况和神经认知评估之间的关系,重点是记忆。JakCCANDO(Jakarta CMV Cardiovascular ART Cardiovascular ART Neurology Dentistry Ophthalmology)项目招募了以 <200 CD4 + T 细胞/μL开始 ART 的患者(年龄 18-48 岁) 。认知评估使用五个领域的验证测试。流式细胞术用于评估 Vδ2 的比例-和 Vδ2 + γδ T 细胞,以及它们的激活 (HLA-DR) 和终末分化 (CD27 - /CD45RA + )。所有患者都携带高水平的与 CMV 反应的抗体,因此在 ART 之前检测 CMV DNA 用于将参与者分为具有中度/高度或极高 CMV 负荷的亚组。在 ART 之前和 6 个月时,与健康对照相比,患者的 Vδ2 - γδ T 细胞比例更高, Vδ2 + γδ T 细胞比例更低。记忆功能的 Z 分数与 Vδ2 +的比例相关两个时间点的 γδ T 细胞。线性回归分析证实了这种关联。当使用 CMV DNA 检测对队列进行分层时,记忆 Z 评分与 Vδ2 + γδ T 细胞或 CMV 抗体之间的关联仅在 CMV 负荷较低的患者中可见。因此,CMV 和 Vδ2 + γδ T 细胞值得进一步考虑,作为可能导致 ART 记忆恢复不良的因素。
更新日期:2022-09-14
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