Fombellida-Lopez Céline, Aguilar Ortmans Diego, Moutschen Michel, Pasternak Alexander O, Darcis Gilles
Immunology and Infectious Diseases Laboratory, Grappe Interdisciplinaire de Génoprotéomique Appliquée (GIGA)-Institute, University of Liège, Liège, Belgium.
General Internal Medicine and Infectious Diseases Department, University Hospital of Liège, Liège, Belgium.
Front Immunol. 2025 Jul 28;16:1628086. doi: 10.3389/fimmu.2025.1628086. eCollection 2025.
Despite effective antiretroviral therapy (ART), people with HIV (PWH) experience persistent immune activation and inflammation, increasing the risk of non-AIDS-related comorbidities. The contribution of the HIV reservoir to this chronic inflammatory state remains debated. Understanding the relationship between HIV persistence, immune activation, and inflammation is crucial for optimizing long-term therapeutic strategies.
This study assessed HIV persistence, immune activation, and systemic inflammation in 49 PWH treated with the same dolutegravir-based triple ART regimen. HIV reservoir size and activity were evaluated by measuring total HIV DNA in peripheral blood mononuclear cells (PBMCs) and rectal tissue, cell-associated (CA) unspliced (US) HIV RNA, and residual viremia. Over 20 inflammatory biomarkers, including sCD14, IL-6, TNF-α, and CXCL10, were analyzed, along with comprehensive immune profiling using a 26-color spectral flow cytometry panel. Clinical parameters such as age, nadir CD4 count, and co-infections were also considered.
Our findings showed a limited association between HIV persistence markers and systemic inflammation or immune activation. Compared to previous studies, participants had lower reservoir sizes and transcriptional activity, likely due to early ART initiation and prolonged suppression. Immune preservation was evident, with high CD4/CD8 ratios and reduced activation markers. These results challenge the idea that the HIV reservoir is the primary driver of chronic inflammation in PWH on a dolutegravir-based long-term ART. Instead, the reservoir may evolve toward a more transcriptionally silent and defective state, reducing its impact on systemic immune activation.
尽管有有效的抗逆转录病毒疗法（ART），但感染艾滋病毒的人（PWH）仍经历持续的免疫激活和炎症，增加了非艾滋病相关合并症的风险。艾滋病毒储存库对这种慢性炎症状态的作用仍存在争议。了解艾滋病毒持续存在、免疫激活和炎症之间的关系对于优化长期治疗策略至关重要。
本研究评估了49名接受相同基于多替拉韦的三联ART方案治疗的PWH的艾滋病毒持续存在、免疫激活和全身炎症。通过测量外周血单核细胞（PBMC）和直肠组织中的总艾滋病毒DNA、细胞相关（CA）未剪接（US）艾滋病毒RNA和残余病毒血症来评估艾滋病毒储存库的大小和活性。分析了20多种炎症生物标志物，包括可溶性CD14、白细胞介素-6、肿瘤坏死因子-α和CXC趋化因子配体10，并使用26色光谱流式细胞术面板进行全面的免疫分析。还考虑了年龄、最低CD4细胞计数和合并感染等临床参数。
我们的研究结果表明，艾滋病毒持续存在标志物与全身炎症或免疫激活之间的关联有限。与先前的研究相比，参与者的储存库大小和转录活性较低，这可能是由于早期开始ART和长期抑制。免疫保存明显，CD4/CD8比率高且激活标志物减少。这些结果挑战了这样一种观点，即艾滋病毒储存库是接受基于多替拉韦的长期ART治疗的PWH慢性炎症的主要驱动因素。相反，储存库可能会朝着转录更沉默和有缺陷的状态发展，从而降低其对全身免疫激活的影响。
