Vassallo Matteo, Durant Jacques, Addou Sami, Ticchioni Michel, Fabre Roxane, Chirio David, Naqvi Alissa, Cua Eric, Ameil Leslie, Godemert Maeva, Pradier Christian, Carles Michel
Internal Medicine/Infectious Diseases Department, Cannes, France.
Infectious Diseases Department, University of Nice, Nice, France.
Front Med (Lausanne). 2025 Apr 15;12:1562537. doi: 10.3389/fmed.2025.1562537. eCollection 2025.
The CD4/CD8 ratio has emerged as a useful indicator of immune dysfunction and comorbid conditions in people living with HIV (PLWH). However, its optimal cut-off value is unclear. We explored the correlation between the CD4/CD8 ratio, immunosenescence markers and comorbid conditions.
We prospectively included PLWH on successful and stable ART (antiretroviral therapy) > 60 years old and receiving either BIC/FTC/TAF or DTG/3TC, in Nice, France. HIV-negative healthy subjects were included as controls. We measured T-cell subsets (naïve, central memory, effector memory and terminally differentiated cells) and the distribution of KLRG1 + CD57+ senescent cells. We correlated CD4/CD8 ratio, background measurements and comorbid conditions.
We included 68 PLWH (median age 69 years, 31 years on ART, median CD4/CD8 ratio 0.76). PLWH had higher levels of senescence markers than controls ( = 8). Among PLWH, adjusting for age, gender, HIV follow-up and duration on ART, those with a CD4/CD8 ratio < 0.76 had more senescent CD8+ cells (AdjOR = 0.93, 95%CI = [0.88; 0.97], -value = 0.003). Higher levels of CD8+ senescence persisted for lower CD4/CD8 ratios, with, in addition, a significant decrease in NK cells in case of a ratio < 0.4. After adjustment, CD8+ effector memory senescent cells were significantly more abundant in PLWH with hypertension.
PLWH on successful ART display elevated immunosenescence markers, mainly on CD8+ T-cells. A CD4/CD8 cut-off value below 0.4 showed the strongest association with immune dysfunction, including NK+ cells. Such results could be useful for identifying patients requiring closer follow-up and screening for complications.
CD4/CD8 比值已成为评估人类免疫缺陷病毒感染者（PLWH）免疫功能障碍和合并症的一个有用指标。然而，其最佳临界值尚不清楚。我们探讨了 CD4/CD8 比值、免疫衰老标志物与合并症之间的相关性。
我们前瞻性纳入了法国尼斯年龄大于 60 岁且接受 BIC/FTC/TAF 或 DTG/3TC 治疗且抗逆转录病毒治疗（ART）成功且稳定的 PLWH。纳入 HIV 阴性健康受试者作为对照。我们测量了 T 细胞亚群（初始 T 细胞、中枢记忆 T 细胞、效应记忆 T 细胞和终末分化细胞）以及 KLRG1+CD57+衰老细胞的分布。我们将 CD4/CD8 比值、背景测量值与合并症进行了相关性分析。
我们纳入了 68 例 PLWH（中位年龄 69 岁，接受 ART 治疗 31 年，中位 CD4/CD8 比值 0.76）。PLWH 的衰老标志物水平高于对照组（=8）。在 PLWH 中，调整年龄、性别、HIV 随访时间和 ART 治疗时长后，CD4/CD8 比值<0.76 的患者有更多衰老的 CD8+细胞（调整后的比值比=0.93，95%置信区间=[0.88; 0.97]，P 值=0.003）。较低的 CD4/CD8 比值持续与较高水平的 CD8+衰老相关，此外，比值<0.4 时自然杀伤细胞显著减少。调整后，高血压 PLWH 中 CD8+效应记忆衰老细胞明显更多。
接受成功 ART 治疗的 PLWH 显示出免疫衰老标志物升高，主要表现在 CD8+T 细胞上。CD4/CD8 临界值低于 0.4 与免疫功能障碍（包括 NK+细胞）的关联最强。这些结果可能有助于识别需要密切随访和筛查并发症的患者。
