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. 2023 Oct 18;228(8):1071-1079.
doi: 10.1093/infdis/jiad229.

Increased Peripheral Inflammation Is Associated With Structural Brain Changes and Reduced Blood Flow in People With Virologically Controlled HIV

Tricia H Burdo  1 , Jake A Robinson  1 , Sarah Cooley  2 , Mandy D Smith  1 , Jacqueline Flynn  1 , Kalen J Petersen  2 , Brittany Nelson  2 , Elizabeth Westerhaus  2 , Julie Wisch  2 , Beau M Ances  2
Affiliations

Increased Peripheral Inflammation Is Associated With Structural Brain Changes and Reduced Blood Flow in People With Virologically Controlled HIV

Tricia H Burdo et al. J Infect Dis. .

Abstract

Background: While antiretroviral therapy (ART) has improved outcomes for people with HIV (PWH), brain dysfunction is still evident. Immune activation and inflammation remain elevated in PWH receiving ART, thereby contributing to morbidity and mortality. Previous studies demonstrated reduced functional and structural changes in PWH; however, underlying mechanisms remain elusive.

Methods: Our cohort consisted of PWH with ART adherence and viral suppression ( < 50 copies/mL; N = 173). Measurements included immune cell markers of overall immune health (CD4/CD8 T-cell ratio) and myeloid inflammation (CD16+ monocytes), plasma markers of inflammatory status (soluble CD163 and CD14), and structural and functional neuroimaging (volume and cerebral blood flow [CBF], respectively).

Results: Decreased CD4/CD8 ratios correlated with reduced brain volume, and higher levels of inflammatory CD16+ monocytes were associated with reduced brain volume in total cortex and gray matter. An increase in plasma soluble CD14-a marker of acute peripheral inflammation attributed to circulating microbial products-was associated with reduced CBF within the frontal, parietal, temporal, and occipital cortices and total gray matter.

Conclusions: CD4/CD8 ratio and number of CD16+ monocytes, which are chronic immune cell markers, are associated with volumetric loss in the brain. Additionally, this study shows a potential new association between plasma soluble CD14 and CBF.

Keywords: HIV; brain; inflammation; neuroimaging.

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Conflict of interest statement

Potential conflicts of interest. T. H. B. has equity in and is a member of the scientific advisory board of Excision BioTherapeutics, Inc, outside of this work. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Figure 1.
Figure 1.
Lower CD4/CD8 ratio and higher CD16+ inflammatory monocytes correlate with lower brain volume. The CD4/CD8 ratio of T lymphocytes was compared with total cortex and gray matter volumes in people with HIV. A, Cortex volume was positively correlated with CD4/CD8 ratio (P = .04, rs = 0.19). B, Total gray matter volume was positively correlated with CD4/CD8 ratio (P = .02, rs = 0.21). C, Cortex volume did not correlate with the percentage of CD16+ inflammatory monocytes (not significant). D, Total gray matter volume was negatively correlated with the CD16+ inflammatory monocytes (P = .03, rs = −0.20). For associations with significant Spearman correlations, the trend is represented as a linear regression trendline.
Figure 2.
Figure 2.
Elevated plasma sCD14 correlates with reduced CBF. Plasma sCD14 was compared with the CBF of frontal, parietal, temporal, and occipital cortical regions and gray matter. A–E, CBF measures of the frontal, parietal, temporal, and occipital cortex and gray matter were all negatively correlated with the plasma sCD14. For associations with significant Spearman correlations, the trend is represented as a linear regression trendline. CBF, cerebral blood flow; sCD14, soluble CD14.
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References

    1. Heaton RK, Clifford DB, Franklin DR, et al. HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy: CHARTER study. Neurology 2010; 75:2087–96. - PMC - PubMed
    1. Gabuzda D, Jamieson BD, Collman RG, et al. Pathogenesis of aging and age-related comorbidities in people with HIV: highlights from the HIV ACTION workshop. Pathog Immun 2020; 5:143–74. - PMC - PubMed
    1. McArthur JC, Johnson TP. Chronic inflammation mediates brain injury in HIV infection: relevance for cure strategies. Curr Opin Neurol 2020; 33:397–404. - PMC - PubMed
    1. Bandera A, Taramasso L, Bozzi G, et al. HIV-associated neurocognitive impairment in the modern ART era: are we close to discovering reliable biomarkers in the setting of virological suppression? Front Aging Neurosci 2019; 11:187. - PMC - PubMed
    1. McBride JA, Striker R. Imbalance in the game of T cells: what can the CD4/CD8 T-cell ratio tell US about HIV and health? PLoS Pathog 2017; 13:e1006624. - PMC - PubMed

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