背景:在抗逆转录病毒治疗(ART)下,约10%的HIV(PWH)患者表现出低水平的病毒血症(LLV)。然而,它的起源和临床意义在很大程度上是未知的,特别是在50至200拷贝/mL之间的病毒学和基于整合酶链转移抑制剂(INSTIs)的现代ART下。我们的目的是表征与病毒血症抑制(SV)和非HIV对照(NHC)的个体相比,他们对HIV的免疫反应较差。
方法:在81名匹配参与者中进行横向观察研究:27PWH与LLV,27带SV的PWH,27NHC激活(CD25,HLA-DR,和CD38)和衰老[CD57,PD1和HAVCR2(TIM3)]通过光谱流式细胞术在外周T细胞亚群中进行了表征。通过免疫测定评估了45种系统性炎症的可溶性生物标志物。细胞频率和血浆生物标志物组间的差异通过广义加性模型评估位置,scale,和形状(GAMLSS)和广义线性模型(GLM),按年龄调整,出生时的性别,和ART方案。
结果:中位年龄为53岁,77.8%为男性。与NHC相比,PWH显示较低的CD4+/CD8+比率和增加的活化,衰老,和炎症,在LLV中突出显示IL-13。此外,与SV相比,LLV显示CD8+幼稚和效应记忆(EM)1型的频率呈下降趋势,伴随着CD4+和CD8+EM和终末分化效应记忆RA+(TEMRA)亚群的更高激活和衰老。在PWH组之间没有观察到系统性炎症的显著差异。
结论:50至200拷贝/mL的LLV会导致细胞毒性活性降低和T细胞功能障碍,从而影响细胞因子的产生,无法控制和消除受感染的细胞。衰老标记物的增加表明免疫记忆的进行性丧失和免疫细胞增殖能力的降低。这种加速的免疫老化可能导致未来合并症的风险增加。这些发现强烈主张加强对这些PWH的监测,以及时识别潜在的未来并发症。
BACKGROUND: 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).
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.