Distinct effects of SSRIs and SNRIs on Soluble Biomarkers in Blood and Cerebrospinal Fluid of people with HIV.

ACE inhibitors HIV SNRIs SSRIs Statins antidepressants chronic inflammation co-medications immune-modulation neurodegeneration

Journal

The Journal of infectious diseases
ISSN: 1537-6613
Titre abrégé: J Infect Dis
Pays: United States
ID NLM: 0413675

Informations de publication

Date de publication:
06 Dec 2023
Historique:
received: 25 09 2023
revised: 13 11 2023
accepted: 04 12 2023
medline: 7 12 2023
pubmed: 7 12 2023
entrez: 7 12 2023
Statut: aheadofprint

Résumé

Persistent inflammation affects people with HIV (PWH) despite antiretroviral therapy (ART). Selective serotonin and serotonin-norepinephrine reuptake inhibitors (SSRIs, SNRIs), HMG-CoA reductase-inhibitors (statins), and angiotensin-converting enzyme inhibitors (ACEIs) have immuno-modulant properties. We evaluated the potential impact of these drugs on inflammation and neurodegeneration in PWH. Cross-sectional single-center (U.S.) analysis in 184 PWH on ART with plasma HIV RNA < 200 cp/mL. All participants had 10 biomarkers measured in blood and cerebrospinal fluid (CSF). To reduce dimensionality, hierarchical clustering and principal components (PCs) analysis were employed. The analyses were adjusted for duration of the drugs and and clinical conditions. Participants were mostly middle-aged men, with median CD4+ T-cells of 620/µL. In adjusted models, SSRI use was associated with three PCs: higher CSF and plasma Aβ42 and CSF CCL2 (aβ=0.14, p = 0.040); lower CSF 8-oxo-dG, total tau, and sCD14 (aβ=-0.12, p = 0.042); higher plasma sCD14 with lower sCD40L (aβ=0.15, p = 0.042). SNRI use was associated with higher values of CSF and plasma neopterin and CSF sTNFR-II (aβ=0.22, p = 0.004). Statins and ACEIs showed no association. SSRIs and SNRIs had distinct biomarker signatures. SSRIs were associated with reduced neurodegeneration, immune activation and oxidative stress in CSF, suggesting a role of SSRIs as adjunctive therapy in PWH.

Sections du résumé

BACKGROUND BACKGROUND
Persistent inflammation affects people with HIV (PWH) despite antiretroviral therapy (ART). Selective serotonin and serotonin-norepinephrine reuptake inhibitors (SSRIs, SNRIs), HMG-CoA reductase-inhibitors (statins), and angiotensin-converting enzyme inhibitors (ACEIs) have immuno-modulant properties. We evaluated the potential impact of these drugs on inflammation and neurodegeneration in PWH.
METHODS METHODS
Cross-sectional single-center (U.S.) analysis in 184 PWH on ART with plasma HIV RNA < 200 cp/mL. All participants had 10 biomarkers measured in blood and cerebrospinal fluid (CSF). To reduce dimensionality, hierarchical clustering and principal components (PCs) analysis were employed. The analyses were adjusted for duration of the drugs and and clinical conditions.
RESULTS RESULTS
Participants were mostly middle-aged men, with median CD4+ T-cells of 620/µL. In adjusted models, SSRI use was associated with three PCs: higher CSF and plasma Aβ42 and CSF CCL2 (aβ=0.14, p = 0.040); lower CSF 8-oxo-dG, total tau, and sCD14 (aβ=-0.12, p = 0.042); higher plasma sCD14 with lower sCD40L (aβ=0.15, p = 0.042). SNRI use was associated with higher values of CSF and plasma neopterin and CSF sTNFR-II (aβ=0.22, p = 0.004). Statins and ACEIs showed no association.
CONCLUSIONS CONCLUSIONS
SSRIs and SNRIs had distinct biomarker signatures. SSRIs were associated with reduced neurodegeneration, immune activation and oxidative stress in CSF, suggesting a role of SSRIs as adjunctive therapy in PWH.

Identifiants

pubmed: 38059529
pii: 7459891
doi: 10.1093/infdis/jiad558
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Auteurs

Mattia Trunfio (M)

HIV Neurobehavioral Research Program, Departments of Neurosciences and Psychiatry, University of California San Diego, CA, USA.
Department of Medical Sciences, University of Turin, Turin, IT.

Bin Tang (B)

HIV Neurobehavioral Research Program, Departments of Neurosciences and Psychiatry, University of California San Diego, CA, USA.

Jennifer E Iudicello (JE)

HIV Neurobehavioral Research Program, Departments of Neurosciences and Psychiatry, University of California San Diego, CA, USA.

Qing Ma (Q)

Department of Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, Buffalo, NY, USA.

Donald R Franklin (DR)

HIV Neurobehavioral Research Program, Departments of Neurosciences and Psychiatry, University of California San Diego, CA, USA.

Debra Cookson (D)

HIV Neurobehavioral Research Program, Departments of Neurosciences and Psychiatry, University of California San Diego, CA, USA.

Patricia K Riggs (PK)

HIV Neurobehavioral Research Program, Departments of Neurosciences and Psychiatry, University of California San Diego, CA, USA.

Mariana Cherner (M)

HIV Neurobehavioral Research Program, Departments of Neurosciences and Psychiatry, University of California San Diego, CA, USA.

David J Moore (DJ)

HIV Neurobehavioral Research Program, Departments of Neurosciences and Psychiatry, University of California San Diego, CA, USA.

Robert K Heaton (RK)

HIV Neurobehavioral Research Program, Departments of Neurosciences and Psychiatry, University of California San Diego, CA, USA.

Scott L Letendre (SL)

HIV Neurobehavioral Research Program, Departments of Neurosciences and Psychiatry, University of California San Diego, CA, USA.

Ronald J Ellis (RJ)

HIV Neurobehavioral Research Program, Departments of Neurosciences and Psychiatry, University of California San Diego, CA, USA.

Classifications MeSH