Sergio Serrano-Villar, Akshay Gala, Peter Bacchetti, Rebecca Hoh, Clara di Germanio, Lillian B Cohn, Timothy J Henrich, Peter W Hunt, Gregory M Laird, Satish K Pillai, Steven G Deeks, Michael J Peluso
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Results Baseline Gal-9 was the most predictive marker for intact HIV kinetics, with lower Gal-9 predicting faster decay over the subsequent seven years. For each 10-fold decrease in Gal-9 at baseline, there was a mean 45% (95%CI 14%-84%) greater decay of intact HIV genomes per year. Conversely, higher baseline ITAC, IL-17, and MIP-1α predicted faster intact HIV decreases. Longitudinal changes in MIP-3α and IL-6 levels strongly associated with intact HIV kinetics, with a 10-fold increase in MIP-3α and a 10-fold decrease in IL-6 associated with a a 9.5% and 10% faster decay of intact HIV genomes per year, respectively. Conclusion The pronounced association between baseline Gal-9 levels and subsequent intact HIV decay suggests that strategies reducing Gal-9 levels could accelerate reservoir decay. Additionally, the correlations of MIP-3α and IL-6 with HIV kinetics indicate a broader cytokine-mediated regulatory network, hinting at multi-targeted interventions that could modulate HIV reservoir dynamics.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Galectin-9 Levels as a Potential Predictor of Intact HIV Reservoir Decay\",\"authors\":\"Sergio Serrano-Villar, Akshay Gala, Peter Bacchetti, Rebecca Hoh, Clara di Germanio, Lillian B Cohn, Timothy J Henrich, Peter W Hunt, Gregory M Laird, Satish K Pillai, Steven G Deeks, Michael J Peluso\",\"doi\":\"10.1093/infdis/jiae426\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Background During antiretroviral therapy (ART), the HIV reservoir exhibits variability as cells with intact genomes decay faster than those with defective genomes, especially in the first years of therapy. The host factors influencing this decay are yet to be characterized. Methods Observational study in 74 PWH on ART, of whom 70 (94.6%) were male. We used the intact proviral DNA assay to measure intact proviruses and Luminex immunoassay to measure 32 inflammatory cytokines in plasma. Linear spline models, with a knot at seven years, evaluated the impact of baseline cytokine levels and their trajectories on intact HIV kinetics over these years. Results Baseline Gal-9 was the most predictive marker for intact HIV kinetics, with lower Gal-9 predicting faster decay over the subsequent seven years. For each 10-fold decrease in Gal-9 at baseline, there was a mean 45% (95%CI 14%-84%) greater decay of intact HIV genomes per year. Conversely, higher baseline ITAC, IL-17, and MIP-1α predicted faster intact HIV decreases. Longitudinal changes in MIP-3α and IL-6 levels strongly associated with intact HIV kinetics, with a 10-fold increase in MIP-3α and a 10-fold decrease in IL-6 associated with a a 9.5% and 10% faster decay of intact HIV genomes per year, respectively. Conclusion The pronounced association between baseline Gal-9 levels and subsequent intact HIV decay suggests that strategies reducing Gal-9 levels could accelerate reservoir decay. Additionally, the correlations of MIP-3α and IL-6 with HIV kinetics indicate a broader cytokine-mediated regulatory network, hinting at multi-targeted interventions that could modulate HIV reservoir dynamics.\",\"PeriodicalId\":501010,\"journal\":{\"name\":\"The Journal of Infectious Diseases\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-08-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"The Journal of Infectious Diseases\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1093/infdis/jiae426\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"The Journal of Infectious Diseases","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1093/infdis/jiae426","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
摘要
背景 在抗逆转录病毒疗法(ART)期间,HIV 病毒库表现出多变性,因为基因组完整的细胞比基因组有缺陷的细胞衰减得更快,尤其是在治疗的最初几年。影响这种衰减的宿主因素尚不明确。方法 对 74 名接受抗逆转录病毒疗法的感染者进行观察研究,其中 70 人(94.6%)为男性。我们使用完整病毒前体 DNA 检测法检测完整病毒前体,并使用 Luminex 免疫测定法检测血浆中的 32 种炎症细胞因子。线性样条模型以 7 年为节点,评估了基线细胞因子水平及其轨迹对这些年完整 HIV 动力学的影响。结果 基线 Gal-9 是最能预测完整 HIV 动力学的标志物,Gal-9 越低,预测其后七年的衰减速度越快。基线 Gal-9 每降低 10 倍,每年完整 HIV 基因组的平均衰减率就会增加 45%(95%CI 14%-84%)。相反,基线 ITAC、IL-17 和 MIP-1α 越高,则完整 HIV 基因组的衰减速度越快。MIP-3α和IL-6水平的纵向变化与完整HIV动力学密切相关,MIP-3α增加10倍和IL-6减少10倍分别与每年完整HIV基因组衰减速度加快9.5%和10%有关。结论 Gal-9 基线水平与随后的完整 HIV 基因组衰减之间的明显关联表明,降低 Gal-9 水平的策略可加速病毒库的衰减。此外,MIP-3α和IL-6与HIV动力学的相关性表明,细胞因子介导的调控网络更为广泛,暗示着多靶点干预措施可以调节HIV库的动态变化。
Galectin-9 Levels as a Potential Predictor of Intact HIV Reservoir Decay
Background During antiretroviral therapy (ART), the HIV reservoir exhibits variability as cells with intact genomes decay faster than those with defective genomes, especially in the first years of therapy. The host factors influencing this decay are yet to be characterized. Methods Observational study in 74 PWH on ART, of whom 70 (94.6%) were male. We used the intact proviral DNA assay to measure intact proviruses and Luminex immunoassay to measure 32 inflammatory cytokines in plasma. Linear spline models, with a knot at seven years, evaluated the impact of baseline cytokine levels and their trajectories on intact HIV kinetics over these years. Results Baseline Gal-9 was the most predictive marker for intact HIV kinetics, with lower Gal-9 predicting faster decay over the subsequent seven years. For each 10-fold decrease in Gal-9 at baseline, there was a mean 45% (95%CI 14%-84%) greater decay of intact HIV genomes per year. Conversely, higher baseline ITAC, IL-17, and MIP-1α predicted faster intact HIV decreases. Longitudinal changes in MIP-3α and IL-6 levels strongly associated with intact HIV kinetics, with a 10-fold increase in MIP-3α and a 10-fold decrease in IL-6 associated with a a 9.5% and 10% faster decay of intact HIV genomes per year, respectively. Conclusion The pronounced association between baseline Gal-9 levels and subsequent intact HIV decay suggests that strategies reducing Gal-9 levels could accelerate reservoir decay. Additionally, the correlations of MIP-3α and IL-6 with HIV kinetics indicate a broader cytokine-mediated regulatory network, hinting at multi-targeted interventions that could modulate HIV reservoir dynamics.