Association of smoking with neurocognition, inflammatory and myeloid cell activation profiles in people with HIV on antiretroviral therapy

Objective: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).Design:We used baseline data on cognition and inflammation from a longitudinal study of virologically suppressed PWH who do and do not smoke.Methods: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.Results: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.Conclusion: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.