Background During antiretroviral therapy (ART), the HIV reservoir shows variability, with cells carrying intact genomes decaying faster than those with defective genomes, particularly in the first years. The host factors influencing this decay remain unclear. Methods Observational study of 74 PWH on ART, 70 (94.6%) of whom were male. Intact proviruses were measured using the intact proviral DNA assay, and 32 inflammatory cytokines were quantified using Luminex immunoassay. Linear spline models assessed the impact of baseline cytokine levels and their trajectories on intact HIV kinetics over seven years. Results Baseline Gal-9 was the strongest predictor, with lower levels predicting faster decay. A 10-fold decrease in baseline Gal-9 correlated with a 45% (95% CI, 14%–84%) greater annual decay of intact HIV genomes. Higher baseline interferon-inducible T-cell α chemoattractant (ITAC), interleukin 17 (IL-17), and macrophage inflammatory protein 1α (MIP-1α) levels also predicted faster decay. Longitudinal increases in MIP-3α and decreases in IL-6 were linked to a 9.5% and 10% faster decay, respectively. Conclusions The association between lower baseline Gal-9 and faster intact HIV decay suggests targeting Gal-9 could enhance reservoir reduction. The involvement of MIP-3α and IL-6 highlights a broader cytokine regulatory network, suggesting potential multi-targeted interventions.

中文翻译：

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半乳糖凝集素 9 水平是完整 HIV 储液库衰变的潜在预测因子


背景 在抗逆转录病毒治疗 （ART） 期间，HIV 宿主表现出可变性，携带完整基因组的细胞比携带基因组缺陷的细胞衰变得更快，尤其是在最初几年。影响这种衰变的宿主因素尚不清楚。方法 对 74 名 PWH 进行 ART 观察性研究，其中 70 名 （94.6%） 为男性。使用完整前病毒 DNA 测定法测量完整前病毒，并使用 Luminex 免疫测定法定量 32 种炎性细胞因子。线性样条模型评估了基线细胞因子水平及其轨迹对 7 年内完整 HIV 动力学的影响。结果 基线 Gal-9 是最强的预测因子，水平越低预测衰减越快。基线 Gal-9 降低 10 倍与完整 HIV 基因组每年衰变 45% （95% CI， 14%–84%） 相关。较高的基线干扰素诱导型 T 细胞α趋化因子 （ITAC） 、白细胞介素 17 （IL-17） 和巨噬细胞炎症蛋白 1α （MIP-1α） 水平也预示着更快的衰变。MIP-3α 的纵向增加和 IL-6 的降低分别与衰减速度加快 9.5% 和 10% 有关。结论 较低基线 Gal-9 与较快的完整 HIV 衰变之间的关联表明靶向 Gal-9 可以增强储库减少。MIP-3α 和 IL-6 的参与突出了更广泛的细胞因子调节网络，表明潜在的多靶点干预措施。