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

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 ART. Design: We used baseline data on cognition and inflammation from a randomized treatment study among smoking and non-smoking PWH. Participants completed 4 neurocognitive tests (7 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, hsCRP, neurofilament light chain (NFL) and monocyte transcriptomes by RNAseq. Results: We recruited 58 PWH (26 smokers, 32 non-smokers). Mean composite and individual neurocognitive scores did not differ significantly by smoking status except for the color shape task; smokers exhibited worse cognitive flexibility, with adjusted mean times 317.2 (95%CI 1.4, 632.9) msec longer than non-smokers. Smokers had higher plasma sCD14 than non-smokers (median(IQR) 1820(1678, 2105) versus 1551(1284, 1760) ng/ml, p=0.009). Other inflammatory markers were not significantly different between smokers and non-smokers. Monocyte transcriptomes showed several functions, regulators and gene sets that differed by smoking status. Conclusions: sCD14, a marker of monocyte activation, is elevated in PWH who smoke. While 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. Overall design: Gene expression profiling by RNA sequencing of monocytes from HIV+/ART smokers and non-smokers