Department of Infectious Diseases, Instituto Nacional de Ciencias Médicas y Nutrición salvador Zubirán, Mexico City, Mexico.
Division of Infectious Diseases, Queen's University, Kingston, Canada Kingston, Canada.
AIDS Res Hum Retroviruses. 2022 Jan;38(1):11-21. doi: 10.1089/AID.2020.0270. Epub 2021 May 5.
We present a cohort of individuals who reached CD4 T cell counts of greater than 1,000 cells/mm (Hypers) after starting antiretroviral treatment (ART) and compared them with those who reached between 350 and 999 CD4 T cells/mm (Concordants). Demographic data, immune recovery kinetics, T CD4 subset phenotypes, and integrated HIV DNA were analyzed. Data from individuals living with HIV on their first ART regimen and after 48 months of follow-up were obtained. Immune phenotype by Flow Cytometry analysis on whole blood was performed, cytokines were measured, and integrated HIV-1 DNA was measured by polymerase chain reaction. From a total of 424 individuals, 26 Hypers (6.1%), 314 Concordants (74.1%), and 84 (19.8%) discordants were identified. Hypers had a higher proportion of CD4-naive (Nv) T cells (37.6 vs. 24.8, < .05), and a low proportion of CD4 effector memory T cells (27.9 vs. 39.4, < .05), with similar results found in CD8 T cells. Hypers demonstrated a higher percentage of CD4CD45RACD31 cells with a lower response to interleukin-2 stimulation and a lower integrated HIV-1 DNA/CD4 ratio (1.2 vs. 2.89, < .05). In Hypers, T cell recovery occurs very early after initiation of ART. Following this initial recovery state, their CD4 T cell level homeostasis seems to be driven by nonthymic-central-Nv cells. This exceptional recovery is associated with a lower HIV reservoir, which may be related to an increase in noninfected CD4 T cells. These patients could then be eligible candidates for cure trials.
我们介绍了一组在开始抗逆转录病毒治疗 (ART) 后 CD4 T 细胞计数超过 1000 个/毫米的个体（超敏组），并将他们与达到 350 至 999 个/毫米 CD4 T 细胞的个体（一致性组）进行了比较。分析了人口统计学数据、免疫恢复动力学、T 细胞 CD4 亚群表型和整合 HIV DNA。获得了首次接受 ART 方案治疗和随访 48 个月后 HIV 感染者的数据。通过全血流式细胞术分析进行免疫表型分析，测量细胞因子，并通过聚合酶链反应测量整合的 HIV-1 DNA。在总共 424 名个体中，确定了 26 名超敏个体（6.1%）、314 名一致性个体（74.1%）和 84 名不匹配个体（19.8%）。超敏组 CD4 幼稚 (Nv) T 细胞的比例较高（37.6% vs. 24.8%， < .05），CD4 效应记忆 T 细胞的比例较低（27.9% vs. 39.4%， < .05），在 CD8 T 细胞中也有类似的结果。超敏组表现出更高比例的 CD4CD45RACD31 细胞，对白细胞介素-2刺激的反应较低，整合的 HIV-1 DNA/CD4 比值较低（1.2 比 2.89， < .05）。在超敏组中，T 细胞在开始 ART 后很快恢复。在这种初始恢复状态之后，他们的 CD4 T 细胞水平似乎由非胸腺中心 Nv 细胞驱动。这种特殊的恢复与较低的 HIV 储存库相关，这可能与未感染的 CD4 T 细胞增加有关。这些患者可能是治愈试验的合格候选者。
