National Center of Microbiology, Institute of Health Carlos III, Madrid, Spain.
Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Institute of Health Carlos III, Madrid, Spain.
J Biomed Sci. 2024 Aug 19;31(1):80. doi: 10.1186/s12929-024-01064-z.
Around 10% of people with HIV (PWH) exhibit a low-level viremia (LLV) under antiretroviral therapy (ART). However, its origin and clinical significance are largely unknown, particularly at viremias between 50 and 200 copies/mL and under modern ART based on integrase strand transfer inhibitors (INSTIs). Our aim was to characterize their poor immune response against HIV in comparison to individuals with suppressed viremia (SV) and non-HIV controls (NHC).
Transversal observational study in 81 matched participants: 27 PWH with LLV, 27 PWH with SV, and 27 NHC. Activation (CD25, HLA-DR, and CD38) and senescence [CD57, PD1, and HAVCR2 (TIM3)] were characterized in peripheral T-cell subsets by spectral flow cytometry. 45 soluble biomarkers of systemic inflammation were evaluated by immunoassays. Differences in cell frequencies and plasma biomarkers among groups were evaluated by a generalized additive model for location, scale, and shape (GAMLSS) and generalized linear model (GLM) respectively, adjusted by age, sex at birth, and ART regimen.
The median age was 53 years and 77.8% were male. Compared to NHC, PWH showed a lower CD4+/CD8+ ratio and increased activation, senescence, and inflammation, highlighting IL-13 in LLV. In addition, LLV showed a downtrend in the frequency of CD8+ naive and effector memory (EM) type 1 compared to SV, along with higher activation and senescence in CD4+ and CD8+ EM and terminally differentiated effector memory RA+ (TEMRA) subpopulations. No significant differences in systemic inflammation were observed between PWH groups.
LLV between 50 and 200 copies/mL leads to reduced cytotoxic activity and T-cell dysfunction that could affect cytokine production, being unable to control and eliminate infected cells. The increase in senescence markers suggests a progressive loss of immunological memory and a reduction in the proliferative capacity of immune cells. This accelerated immune aging could lead to an increased risk of developing future comorbidities. These findings strongly advocate for heightened surveillance of these PWH to promptly identify potential future complications.
约 10%的接受抗逆转录病毒疗法 (ART) 的艾滋病毒感染者 (PWH) 表现出低水平病毒血症 (LLV)。然而，其起源和临床意义在很大程度上尚不清楚，特别是在病毒载量为 50 至 200 拷贝/ml 之间以及基于整合酶链转移抑制剂 (INSTIs) 的现代 ART 下。我们的目的是与抑制病毒血症 (SV) 的个体和非艾滋病毒对照 (NHC) 相比，描述他们对艾滋病毒的免疫反应不良。
在 81 名匹配参与者中进行横断面观察性研究：27 名 PWH 为 LLV，27 名 PWH 为 SV，27 名 NHC。通过光谱流式细胞术在外周 T 细胞亚群中表征激活 (CD25、HLA-DR 和 CD38) 和衰老 [CD57、PD1 和 HAVCR2 (TIM3)]。通过免疫测定评估 45 种系统性炎症的可溶性生物标志物。通过广义加性模型进行位置、比例和形状 (GAMLSS) 和广义线性模型 (GLM) 分别评估组间细胞频率和血浆生物标志物的差异，通过年龄、出生时的性别和 ART 方案进行调整。
中位年龄为 53 岁，77.8%为男性。与 NHC 相比，PWH 的 CD4+/CD8+比例较低，激活、衰老和炎症增加，在 LLV 中突出了 IL-13。此外，与 SV 相比，LLV 表现出 CD8+幼稚和效应记忆 (EM) 1 型的频率呈下降趋势，同时 CD4+和 CD8+EM 和终末分化效应记忆 RA+（TEMRA）亚群的激活和衰老增加。PWH 组之间未观察到系统性炎症的显著差异。
50 至 200 拷贝/ml 之间的 LLV 导致细胞毒性活性和 T 细胞功能障碍降低，这可能影响细胞因子的产生，无法控制和清除感染细胞。衰老标志物的增加表明免疫记忆的逐渐丧失和免疫细胞增殖能力的降低。这种加速的免疫衰老可能导致未来合并症的风险增加。这些发现强烈主张对这些 PWH 进行更高的监测，以迅速识别潜在的未来并发症。
