Low-level HIV-1 viremia affects T-cell activation and senescence in long-term treated adults in the INSTI era.

IF 9 2区 医学 Q1 CELL BIOLOGY Journal of Biomedical Science Pub Date : 2024-08-19 DOI:10.1186/s12929-024-01064-z
Violeta Lara-Aguilar, Manuel Llamas-Adán, Óscar Brochado-Kith, Celia Crespo-Bermejo, Sergio Grande-García, Sonia Arca-Lafuente, Ignacio de Los Santos, Carmen Prado, Mario Alía, Coral Sainz-Pinós, Amanda Fernández-Rodríguez, Luz Martín-Carbonero, Ricardo Madrid, Verónica Briz
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Abstract

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.

Conclusion: 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.

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低水平的 HIV-1 病毒血症会影响 INSTI 时代长期接受治疗的成年人的 T 细胞活化和衰老。
背景:在接受抗逆转录病毒疗法(ART)时,约有 10% 的艾滋病病毒感染者(PWH)会出现低水平病毒血症(LLV)。然而,低水平病毒血症的起源和临床意义在很大程度上还不为人所知,尤其是当病毒血症在 50 到 200 拷贝/毫升之间时,以及在使用整合酶链转移抑制剂(INSTIs)的现代抗逆转录病毒疗法下。我们的目的是与病毒血症抑制(SV)者和非 HIV 对照组(NHC)相比,了解他们对 HIV 的免疫反应低下的特点:方法:对 81 名配对参与者进行横向观察研究:27 名感染 LLV 的 PWH、27 名感染 SV 的 PWH 和 27 名 NHC。通过光谱流式细胞术确定了外周 T 细胞亚群的活化(CD25、HLA-DR 和 CD38)和衰老(CD57、PD1 和 HAVCR2 (TIM3))特征。通过免疫测定评估了全身炎症的 45 种可溶性生物标志物。各组间细胞频率和血浆生物标志物的差异分别通过位置、规模和形状的广义加性模型(GAMLSS)和广义线性模型(GLM)进行评估,并根据年龄、出生时性别和抗逆转录病毒疗法进行调整:中位年龄为 53 岁,77.8% 为男性。与 NHC 相比,PWH 的 CD4+/CD8+ 比率较低,活化、衰老和炎症增加,LLV 中的 IL-13 尤为突出。此外,与SV相比,LLV中CD8+天真型和效应记忆(EM)1型的频率呈下降趋势,CD4+和CD8+ EM以及终末分化效应记忆RA+(TEMRA)亚群的活化和衰老程度较高。PWH组之间的全身炎症没有明显差异:结论:50 至 200 拷贝/毫升的 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,无法控制和消除感染细胞。衰老标志物的增加表明免疫记忆逐渐丧失,免疫细胞的增殖能力下降。这种加速的免疫衰老可能会导致未来罹患合并症的风险增加。这些研究结果强烈建议加强对这些病患的监测,以便及时发现未来可能出现的并发症。
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来源期刊
Journal of Biomedical Science
Journal of Biomedical Science 医学-医学:研究与实验
CiteScore
18.50
自引率
0.90%
发文量
95
审稿时长
1 months
期刊介绍: The Journal of Biomedical Science is an open access, peer-reviewed journal that focuses on fundamental and molecular aspects of basic medical sciences. It emphasizes molecular studies of biomedical problems and mechanisms. The National Science and Technology Council (NSTC), Taiwan supports the journal and covers the publication costs for accepted articles. The journal aims to provide an international platform for interdisciplinary discussions and contribute to the advancement of medicine. It benefits both readers and authors by accelerating the dissemination of research information and providing maximum access to scholarly communication. All articles published in the Journal of Biomedical Science are included in various databases such as Biological Abstracts, BIOSIS, CABI, CAS, Citebase, Current contents, DOAJ, Embase, EmBiology, and Global Health, among others.
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