Yadav Anjana, Gionet Gabrielle, Karaj Antoneta, Kossenkov Andrew V, Kannan Toshitha, Putt Mary E, Stephens Shields Alisa J, Ashare Rebecca L, Collman Ronald G
Department of Medicine.
Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania Perelman School of Medicine.
AIDS. 2024 Dec 1;38(15):2010-2020. doi: 10.1097/QAD.0000000000004015. Epub 2024 Sep 13.
People with HIV (PWH) experience excess comorbidities, including neurocognitive disorders, which are linked to inflammation, particularly monocyte-macrophage activation. Smoking contributes to morbidity and mortality in well treated PWH. We investigated associations between smoking, neurocognitive function, and inflammation in PWH on antiretroviral therapy (ART).
We used baseline data on cognition and inflammation from a longitudinal study of virologically suppressed PWH who do and do not smoke.
Participants completed four neurocognitive tests (seven measures), with a composite score as the primary measure. Inflammatory markers were plasma sCD14, sCD163, and CCL2/MCP-1; %CD14 + monocytes expressing CD16, CD163, and CCR2; and %CD8 + T cells co-expressing CD38/HLA-DR. Exploratory analyses included a plasma cytokine/chemokine panel, neurofilament light chain (NFL), hsCRP, and monocyte transcriptomes by RNAseq.
We recruited 58 PWH [26 current smoking (PWH/S), 32 no current smoking (PWH/NS)]. Mean composite and individual neurocognitive scores did not differ significantly by smoking status except for the color shape task; PWH/S exhibited worse cognitive flexibility, with adjusted mean times 317.2 [95% confidence interval (CI) 1.4-632.9] ms longer than PWH/NS. PWH/S had higher plasma sCD14 than PWH/NS [median (IQR) 1820 (1678-2105) vs. 1551 (1284-1760) ng/ml, P = 0.009]. Other inflammatory markers were not significantly different between PWH/S and PWH/NS. Monocyte transcriptomes showed several functions, regulators, and gene-sets that differed by smoking status.
sCD14, a marker of monocyte activation, is elevated in PWH who smoke. Although neurocognitive measures and other inflammatory markers did not generally differ, these data implicate smoking-related myeloid activation and monocyte gene dysregulation in the HIV/smoking synergy driving HIV-associated comorbidities.
人类免疫缺陷病毒感染者（PWH）存在多种共病，包括神经认知障碍，这些共病与炎症有关，尤其是单核细胞-巨噬细胞激活。吸烟会增加接受良好治疗的PWH的发病率和死亡率。我们研究了接受抗逆转录病毒治疗（ART）的PWH中吸烟、神经认知功能和炎症之间的关联。
我们使用了一项对病毒学抑制的吸烟和不吸烟PWH的纵向研究中的认知和炎症基线数据。
参与者完成了四项神经认知测试（七项指标），以综合评分作为主要指标。炎症标志物包括血浆可溶性CD14（sCD14）、可溶性CD163（sCD163）和CCL2/单核细胞趋化蛋白-1（MCP-1）；表达CD16、CD163和CCR2的CD14+单核细胞百分比；以及共表达CD38/人类白细胞抗原-DR（HLA-DR）的CD8+T细胞百分比。探索性分析包括血浆细胞因子/趋化因子检测、神经丝轻链（NFL）、高敏C反应蛋白（hsCRP）以及通过RNA测序得到的单核细胞转录组。
我们招募了58名PWH[26名当前吸烟者（PWH/S），32名当前不吸烟者（PWH/NS）]。除颜色形状任务外，平均综合和个体神经认知评分在吸烟状态之间无显著差异；PWH/S表现出较差的认知灵活性，调整后的平均时间比PWH/NS长317.2[95%置信区间（CI）1.4-632.9]毫秒。PWH/S的血浆sCD14高于PWH/NS[中位数（四分位间距）1820（1678-2105）对1551（1284-1760）纳克/毫升，P = 0.009]。PWH/S和PWH/NS之间的其他炎症标志物无显著差异。单核细胞转录组显示了几种因吸烟状态而异的功能、调节因子和基因集。
sCD14是单核细胞激活的标志物，在吸烟的PWH中升高。尽管神经认知指标和其他炎症标志物通常无差异，但这些数据表明，在导致HIV相关共病的HIV/吸烟协同作用中，吸烟相关的髓系激活和单核细胞基因失调起了作用。
