Plasma metabolomic profile is near-normal in people with HIV on long-term suppressive antiretroviral therapy

BackgroundCombination antiretroviral therapy (ART) has transformed human immunodeficiency virus (HIV) infection in people with HIV (PWH). However, a chronic state of immune activation and inflammation is maintained despite achieving HIV suppression and satisfactory immunological recovery. We aimed t...

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Main Authors: Ana Virseda-Berdices, Rubén Martín-Escolano, Juan Berenguer, Juan González-García, Oscar Brochado-Kith, David Rojo, Amanda Fernández-Rodríguez, Leire Pérez-Latorre, Victor Hontañón, Coral Barbas, Salvador Resino, María Ángeles Jiménez-Sousa
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-03-01
Series:Frontiers in Cellular and Infection Microbiology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fcimb.2024.1340610/full
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author Ana Virseda-Berdices
Ana Virseda-Berdices
Rubén Martín-Escolano
Rubén Martín-Escolano
Juan Berenguer
Juan Berenguer
Juan Berenguer
Juan González-García
Juan González-García
Juan González-García
Oscar Brochado-Kith
Oscar Brochado-Kith
David Rojo
Amanda Fernández-Rodríguez
Amanda Fernández-Rodríguez
Leire Pérez-Latorre
Leire Pérez-Latorre
Leire Pérez-Latorre
Victor Hontañón
Victor Hontañón
Victor Hontañón
Coral Barbas
Salvador Resino
Salvador Resino
María Ángeles Jiménez-Sousa
María Ángeles Jiménez-Sousa
author_facet Ana Virseda-Berdices
Ana Virseda-Berdices
Rubén Martín-Escolano
Rubén Martín-Escolano
Juan Berenguer
Juan Berenguer
Juan Berenguer
Juan González-García
Juan González-García
Juan González-García
Oscar Brochado-Kith
Oscar Brochado-Kith
David Rojo
Amanda Fernández-Rodríguez
Amanda Fernández-Rodríguez
Leire Pérez-Latorre
Leire Pérez-Latorre
Leire Pérez-Latorre
Victor Hontañón
Victor Hontañón
Victor Hontañón
Coral Barbas
Salvador Resino
Salvador Resino
María Ángeles Jiménez-Sousa
María Ángeles Jiménez-Sousa
author_sort Ana Virseda-Berdices
collection DOAJ
description BackgroundCombination antiretroviral therapy (ART) has transformed human immunodeficiency virus (HIV) infection in people with HIV (PWH). However, a chronic state of immune activation and inflammation is maintained despite achieving HIV suppression and satisfactory immunological recovery. We aimed to determine whether the plasma metabolomic profile of PWH on long-term suppressive ART and immunologically recovered approximates the normality by comparison with healthy controls with similar age and gender.MethodsWe carried out a cross-sectional study in 17 PWH on long-term ART (HIV-RNA <50 copies/mL, CD4+ ≥500 cells/mm3, and CD4+/CD8+ ≥1) and 19 healthy controls with similar age and gender. Metabolomics analysis was performed by gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS). The statistical association analysis was performed by principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and Generalized Linear Models (GLM) with a gamma distribution (log-link). Significance levels (p-value) were corrected for multiple testing (q-value).ResultsPCA and PLS-DA analyses found no relevant differences between groups. Adjusted GLM showed 14 significant features (q-value<0.20), of which only three could be identified: lysophosphatidylcholine (LysoPC) (22:6) (q-value=0.148), lysophosphatidylethanolamine (LysoPE) (22:6) (q-value=0.050) and hydroperoxy-octadecatrienoic acid (HpOTrE)/dihydroperoxy-octadecatrienoic acid (DiHOTrE)/epoxy-octadecadienoic acid (EpODE) (q-value=0.136). These significant identified metabolites were directly correlated to plasma inflammatory biomarkers in PWH and negatively correlated in healthy controls.ConclusionPWH on long-term ART have a metabolomic profile that is almost normal compared to healthy controls. Nevertheless, residual metabolic alterations linked to inflammatory biomarkers persist, which could favor the development of age-related comorbidities among this population.
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spelling doaj.art-a981598b0b5349df940145cfb0e1f6542024-03-14T04:49:06ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882024-03-011410.3389/fcimb.2024.13406101340610Plasma metabolomic profile is near-normal in people with HIV on long-term suppressive antiretroviral therapyAna Virseda-Berdices0Ana Virseda-Berdices1Rubén Martín-Escolano2Rubén Martín-Escolano3Juan Berenguer4Juan Berenguer5Juan Berenguer6Juan González-García7Juan González-García8Juan González-García9Oscar Brochado-Kith10Oscar Brochado-Kith11David Rojo12Amanda Fernández-Rodríguez13Amanda Fernández-Rodríguez14Leire Pérez-Latorre15Leire Pérez-Latorre16Leire Pérez-Latorre17Victor Hontañón18Victor Hontañón19Victor Hontañón20Coral Barbas21Salvador Resino22Salvador Resino23María Ángeles Jiménez-Sousa24María Ángeles Jiménez-Sousa25Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología (CNM), Instituto de Salud Carlos III (ISCIII), Madrid, SpainCentro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, SpainUnidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología (CNM), Instituto de Salud Carlos III (ISCIII), Madrid, SpainCentro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, SpainCentro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, SpainUnidad de Enfermedades Infecciosas/VIH, Hospital General Universitario “Gregorio Marañón”, Madrid, SpainInstituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, SpainCentro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, SpainServicio de Medicina Interna-Unidad de VIH, Hospital Universitario La Paz, Madrid, SpainInstituto de Investigación Sanitaria La Paz (IdiPAZ), Madrid, SpainUnidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología (CNM), Instituto de Salud Carlos III (ISCIII), Madrid, SpainCentro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, SpainCentre of Metabolomics and Bioanalysis (CEMBIO), Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Boadilla del Monte, SpainUnidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología (CNM), Instituto de Salud Carlos III (ISCIII), Madrid, SpainCentro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, SpainCentro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, SpainUnidad de Enfermedades Infecciosas/VIH, Hospital General Universitario “Gregorio Marañón”, Madrid, SpainInstituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, SpainCentro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, SpainServicio de Medicina Interna-Unidad de VIH, Hospital Universitario La Paz, Madrid, SpainInstituto de Investigación Sanitaria La Paz (IdiPAZ), Madrid, SpainCentre of Metabolomics and Bioanalysis (CEMBIO), Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Boadilla del Monte, SpainUnidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología (CNM), Instituto de Salud Carlos III (ISCIII), Madrid, SpainCentro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, SpainUnidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología (CNM), Instituto de Salud Carlos III (ISCIII), Madrid, SpainCentro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, SpainBackgroundCombination antiretroviral therapy (ART) has transformed human immunodeficiency virus (HIV) infection in people with HIV (PWH). However, a chronic state of immune activation and inflammation is maintained despite achieving HIV suppression and satisfactory immunological recovery. We aimed to determine whether the plasma metabolomic profile of PWH on long-term suppressive ART and immunologically recovered approximates the normality by comparison with healthy controls with similar age and gender.MethodsWe carried out a cross-sectional study in 17 PWH on long-term ART (HIV-RNA <50 copies/mL, CD4+ ≥500 cells/mm3, and CD4+/CD8+ ≥1) and 19 healthy controls with similar age and gender. Metabolomics analysis was performed by gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS). The statistical association analysis was performed by principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and Generalized Linear Models (GLM) with a gamma distribution (log-link). Significance levels (p-value) were corrected for multiple testing (q-value).ResultsPCA and PLS-DA analyses found no relevant differences between groups. Adjusted GLM showed 14 significant features (q-value<0.20), of which only three could be identified: lysophosphatidylcholine (LysoPC) (22:6) (q-value=0.148), lysophosphatidylethanolamine (LysoPE) (22:6) (q-value=0.050) and hydroperoxy-octadecatrienoic acid (HpOTrE)/dihydroperoxy-octadecatrienoic acid (DiHOTrE)/epoxy-octadecadienoic acid (EpODE) (q-value=0.136). These significant identified metabolites were directly correlated to plasma inflammatory biomarkers in PWH and negatively correlated in healthy controls.ConclusionPWH on long-term ART have a metabolomic profile that is almost normal compared to healthy controls. Nevertheless, residual metabolic alterations linked to inflammatory biomarkers persist, which could favor the development of age-related comorbidities among this population.https://www.frontiersin.org/articles/10.3389/fcimb.2024.1340610/fullantiretroviral therapyCD4+/CD8+ ratioHIVinflammationmetabolomics
spellingShingle Ana Virseda-Berdices
Ana Virseda-Berdices
Rubén Martín-Escolano
Rubén Martín-Escolano
Juan Berenguer
Juan Berenguer
Juan Berenguer
Juan González-García
Juan González-García
Juan González-García
Oscar Brochado-Kith
Oscar Brochado-Kith
David Rojo
Amanda Fernández-Rodríguez
Amanda Fernández-Rodríguez
Leire Pérez-Latorre
Leire Pérez-Latorre
Leire Pérez-Latorre
Victor Hontañón
Victor Hontañón
Victor Hontañón
Coral Barbas
Salvador Resino
Salvador Resino
María Ángeles Jiménez-Sousa
María Ángeles Jiménez-Sousa
Plasma metabolomic profile is near-normal in people with HIV on long-term suppressive antiretroviral therapy
Frontiers in Cellular and Infection Microbiology
antiretroviral therapy
CD4+/CD8+ ratio
HIV
inflammation
metabolomics
title Plasma metabolomic profile is near-normal in people with HIV on long-term suppressive antiretroviral therapy
title_full Plasma metabolomic profile is near-normal in people with HIV on long-term suppressive antiretroviral therapy
title_fullStr Plasma metabolomic profile is near-normal in people with HIV on long-term suppressive antiretroviral therapy
title_full_unstemmed Plasma metabolomic profile is near-normal in people with HIV on long-term suppressive antiretroviral therapy
title_short Plasma metabolomic profile is near-normal in people with HIV on long-term suppressive antiretroviral therapy
title_sort plasma metabolomic profile is near normal in people with hiv on long term suppressive antiretroviral therapy
topic antiretroviral therapy
CD4+/CD8+ ratio
HIV
inflammation
metabolomics
url https://www.frontiersin.org/articles/10.3389/fcimb.2024.1340610/full
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