Rethinking HIV treatment: How non-integrase strand regimens may hold the key to better immune health.

IF 2.8 3区 医学 Q2 INFECTIOUS DISEASES
HIV Medicine Pub Date : 2025-03-28 DOI:10.1111/hiv.70020
Bogusz Aksak-Wąs, Karolina Skonieczna-Żydecka, Miłosz Parczewski, Rafał Hrynkiewicz, Filip Lewandowski, Karol Serwin, Kaja Mielczak, Franciszek Lenkiewicz, Paulina Niedźwiedzka-Rystwej
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引用次数: 0

Abstract

Purpose: HIV outcome changed drastically with antiretroviral (ARV) therapy, especially after the introduction of second-generation integrase strand transfer inhibitors (INSTIs). Despite these advances, however, chronic immune activation and exhaustion, marked by programmed cell death 1 (PD-1) and programmed death ligand 1 (PD-L1) upregulation, persist in patients. This study investigates the impact of various ARV regimens on these immune exhaustion markers in newly diagnosed HIV patients over 12 months, taking into consideration cardiovascular risk.

Methods: This study included 58 newly diagnosed patients with HIV at Pomeranian Medical University, Szczecin, Poland. Participants received ARV regimens classified as INSTI + tenofovir alafenamide, INSTI + tenofovir disoproxil fumarate, or non-INSTI-based (VARIA). Flow cytometry was used to assess PD-1 and PD-L1 expression on CD3+, CD3+CD4+, CD3+CD8+ and CD19+ lymphocytes. Statistical analyses included Wilcoxon paired tests, Kruskal-Wallis tests and multivariate regression, with validation through residual analysis and linear discriminant analysis (LDA).

Results: INSTI-based regimens were linked to higher PD-1 expression on CD3+ and CD3+CD4+ lymphocytes, indicating increased immune exhaustion. Conversely, non-INSTI regimens were associated with lower PD-1 levels, suggesting better retention of immune function. A positive correlation between cardiovascular risk a prediction model to estimate 10-year fatal and non-fatal cardiovascular disease (SCORE2) and PD-1 expression was observed. However, the modest explanatory power of the models suggests variability in the effects of different ARV regimens.

Conclusion: This study challenges the assumption that INSTI-based ARV regimens are universally superior, suggesting that non-INSTI therapies may better preserve immune function by reducing PD-1 expression. These findings highlight the potential benefits of non-INSTI regimens in improving long-term clinical outcomes in HIV treatment, warranting further research.

重新思考艾滋病毒治疗:非整合酶链方案如何可能成为改善免疫健康的关键。
目的:抗逆转录病毒(ARV)治疗后,特别是引入第二代整合酶链转移抑制剂(INSTIs)后,HIV预后发生了巨大变化。然而,尽管有这些进展,以程序性细胞死亡1 (PD-1)和程序性死亡配体1 (PD-L1)上调为标志的慢性免疫激活和衰竭在患者中持续存在。本研究在考虑心血管风险的情况下,调查了各种ARV治疗方案对新诊断的HIV患者12个月内这些免疫衰竭标志物的影响。方法:本研究纳入了波兰什切青波美拉尼亚医科大学58例新诊断的HIV患者。参与者接受的抗逆转录病毒治疗方案分为INSTI +替诺福韦阿拉那胺、INSTI +富马酸替诺福韦二吡酯或非基于INSTI的(VARIA)。流式细胞术检测PD-1和PD-L1在CD3+、CD3+CD4+、CD3+CD8+和CD19+淋巴细胞上的表达。统计分析包括Wilcoxon配对检验、Kruskal-Wallis检验和多元回归,并通过残差分析和线性判别分析(LDA)进行验证。结果:基于insi的方案与CD3+和CD3+CD4+淋巴细胞上更高的PD-1表达相关,表明免疫衰竭增加。相反,非insti方案与较低的PD-1水平相关,表明免疫功能保留更好。观察到用于估计10年致死性和非致死性心血管疾病的心血管风险预测模型(SCORE2)与PD-1表达呈正相关。然而,这些模型的解释能力有限,表明不同抗逆转录病毒治疗方案的效果存在差异。结论:本研究挑战了基于insti的抗逆转录病毒治疗方案普遍优越的假设,表明非insti治疗可能通过降低PD-1表达来更好地保护免疫功能。这些发现强调了非insti方案在改善HIV治疗的长期临床结果方面的潜在益处,值得进一步研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
HIV Medicine
HIV Medicine 医学-传染病学
CiteScore
5.10
自引率
10.00%
发文量
167
审稿时长
6-12 weeks
期刊介绍: HIV Medicine aims to provide an alternative outlet for publication of international research papers in the field of HIV Medicine, embracing clinical, pharmocological, epidemiological, ethical, preclinical and in vitro studies. In addition, the journal will commission reviews and other feature articles. It will focus on evidence-based medicine as the mainstay of successful management of HIV and AIDS. The journal is specifically aimed at researchers and clinicians with responsibility for treating HIV seropositive patients.
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