BACKGROUND Indoleamine 2,3-dioxygenase (IDO) is an immunoregulatory enzyme that metabolizes tryptophan to immunosuppressive kynurenines. We investigated whether IDO activity is associated with the size of HIV reservoir. METHODS Total human immunodeficiency virus (HIV) DNA in peripheral blood mononuclear cells (PBMCs) from 127 HIV-infected patients receiving antiretroviral therapy (ART) was quantified. Tryptophan and kynurenine concentrations, as well as microbial translocation markers, were measured in plasma samples. T-cell activation and exhaustion in PBMCs were assessed by flow cytometry. RESULTS Elevated IDO activity prior to ART correlated with on-ART HIV DNA (r = 0.35, P = .004), but was not associated with pre-ART HIV DNA. A median duration of 15 months of ART significantly decreased IDO activity; however, these levels were still higher than those observed in HIV-uninfected controls. Among treated participants, IDO activity positively correlated with their concurrent HIV DNA (r = 0.36, P < .0001). Multivariate model showed an independent association of pre-ART CD4/CD8 ratio (adjusted odds ratio [aOR], 0.75 per 0.1 increase [95% confidence interval {CI}, .62-.91]) and on-ART IDO activity (aOR, 1.09 per nM/μM increase [95% CI, 1.04-1.14]) with higher levels of HIV DNA on-ART. A lack of association of the microbial translocation markers was observed with the size of HIV reservoir. HIV DNA positively correlated with the proportions of activated CD4 T and CD8 T cells and exhausted CD4 T cells. CONCLUSIONS We observed a positive correlation between IDO activity and total HIV DNA in blood, highlighting the important role of immunometabolic aberrations in HIV persistence.

中文翻译：

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血浆吲哚胺2，3-双加氧酶活性与接受抗逆转录病毒疗法的患者的人类免疫缺陷病毒库的大小有关。

背景技术吲哚胺2，3-二加氧酶（IDO）是一种免疫调节酶，其将色氨酸代谢成免疫抑制性犬尿氨酸。我们调查了IDO活动是否与HIV储存库的大小有关。方法对127例接受抗逆转录病毒治疗（ART）的HIV感染患者的外周血单个核细胞（PBMC）中的总人类免疫缺陷病毒（HIV）DNA进行定量。在血浆样品中测量了色氨酸和犬尿氨酸的浓度，以及微生物易位标记。通过流式细胞术评估PBMC中的T细胞活化和衰竭。结果ART之前IDO活性升高与ART上的HIV DNA相关（r = 0.35，P = .004），但与ART之前的HIV DNA不相关。中位时间为15个月的ART显着降低了IDO活性；然而，这些水平仍高于未感染艾滋病毒的对照中观察到的水平。在接受治疗的参与者中，IDO活性与其并发的HIV DNA呈正相关（r = 0.36，P <.0001）。多变量模型显示，ART-ART前CD4 / CD8比率（调整后的优势比[aOR]，0.75 / 0.1增加[95％置信区间{CI} 、. 62-.91]）与ART IDO活性（aOR）具有独立的关联，随着nART / HIV基因水平的升高，每nM /μM增加1.09 [95％CI，1.04-1.14]。观察到微生物易位标记与HIV储存库的大小缺乏关联。HIV DNA与活化的CD4 T和CD8 T细胞以及耗尽的CD4 T细胞的比例呈正相关。结论我们观察到IDO活性与血液中总HIV DNA呈正相关，