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.