Circulating levels of inflammatory mediators in pregnant people living with HIV according to antiretroviral therapy regimen
IntroductionThe use of antiretroviral therapy (ART) during pregnancy, particularly protease-inhibitor-based regimens (PI), has been linked to adverse outcomes including preterm delivery. As this outcome may be related to systemic inflammation, we sought to characterize inflammatory profiles of pregn...
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Frontiers Media S.A.
2024-01-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2023.1282291/full |
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author | Stephanie Hindle Stephanie Hindle Sylvie Girard Sylvie Girard Sylvie Girard Sylvie Girard Helene C. F. Cote Helene C. F. Cote Helene C. F. Cote Deborah Money Deborah Money Evelyn Mann Evelyn Mann Isabelle Boucoiran Isabelle Boucoiran Isabelle Boucoiran for the Children and Women Antiretroviral Therapy and Makers of Aging (Carma) Preg Team |
author_facet | Stephanie Hindle Stephanie Hindle Sylvie Girard Sylvie Girard Sylvie Girard Sylvie Girard Helene C. F. Cote Helene C. F. Cote Helene C. F. Cote Deborah Money Deborah Money Evelyn Mann Evelyn Mann Isabelle Boucoiran Isabelle Boucoiran Isabelle Boucoiran for the Children and Women Antiretroviral Therapy and Makers of Aging (Carma) Preg Team |
author_sort | Stephanie Hindle |
collection | DOAJ |
description | IntroductionThe use of antiretroviral therapy (ART) during pregnancy, particularly protease-inhibitor-based regimens (PI), has been linked to adverse outcomes including preterm delivery. As this outcome may be related to systemic inflammation, we sought to characterize inflammatory profiles of pregnant people living with HIV (PLWH) by comparing their levels of inflammatory mediators at two timepoints during pregnancy according to ART regimen, and to HIV-negative controls.MethodsSecond and third trimester samples from 144 pregnant PLWH treated with ART and 24 HIV-uninfected controls were retrieved from the CARMA-PREG cohort. Peripheral plasma levels of 12 inflammatory mediators previously linked to HIV infection and/or poor pregnancy outcomes were quantified by multiplex assay: HMGB1, GM-CSF, IFNα, IFNβ, IFNγ, IL-10, IL-17, IL-1β, IL-6, TNFα, AGP, and CRP. Levels were compared by ART regimen and HIV status.ResultsAdjusted analyses showed that PLWH have higher levels of AGP throughout pregnancy and lower levels of IFNγ and IL-1β during the second trimester. PI-based regimens are associated with significantly higher levels of IFNα and IL-17 during the second trimester and IFNα, CRP, HMGB1, and IFNβ during the third trimester compared to InSTI-based regimens. The PI-subgroup was associated with preterm delivery and higher HIV-1 viral load.DiscussionOur results suggest that PI-based regimens are associated with a pro-inflammatory and antiviral immunological response and a high viral load, which may be a mechanism through which PI-based regimens increase the risk of preterm delivery. Further investigations into cellular mechanisms and pro-inflammatory cascades leading to preterm delivery are necessary to support this association. |
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issn | 1664-302X |
language | English |
last_indexed | 2024-03-08T16:05:29Z |
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spelling | doaj.art-653f7f46f55840b88ebefd037862b6aa2024-01-08T06:10:50ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2024-01-011410.3389/fmicb.2023.12822911282291Circulating levels of inflammatory mediators in pregnant people living with HIV according to antiretroviral therapy regimenStephanie Hindle0Stephanie Hindle1Sylvie Girard2Sylvie Girard3Sylvie Girard4Sylvie Girard5Helene C. F. Cote6Helene C. F. Cote7Helene C. F. Cote8Deborah Money9Deborah Money10Evelyn Mann11Evelyn Mann12Isabelle Boucoiran13Isabelle Boucoiran14Isabelle Boucoiran15for the Children and Women Antiretroviral Therapy and Makers of Aging (Carma) Preg TeamDepartment of Pharmacology and Physiology, Université de Montréal, Montréal, QC, CanadaCHU Sainte-Justine Research Center, Montréal, QC, CanadaCHU Sainte-Justine Research Center, Montréal, QC, CanadaDepartment of Obstetrics and Gynecology, Université de Montréal, Montréal, QC, CanadaDepartment of Microbiology, Infectiology and Immunology, Université de Montréal, Montréal, QC, CanadaDepartment of Obstetrics and Gynecology and Department of Immunology, Mayo Clinic, Rochester, MN, United StatesDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, CanadaCentre for Blood Research, University of British Columbia, Vancouver, BC, CanadaWomen’s Health Research Institute, Vancouver, BC, CanadaWomen’s Health Research Institute, Vancouver, BC, CanadaDepartment of Obstetrics and Gynecology, University of British Columbia, Vancouver, BC, CanadaWomen’s Health Research Institute, Vancouver, BC, Canada0Oak Tree Clinic, BC Women's Hospital and Health Centre, Vancouver, BC, CanadaCHU Sainte-Justine Research Center, Montréal, QC, CanadaDepartment of Obstetrics and Gynecology, Université de Montréal, Montréal, QC, Canada1School of Public Health, Université de Montréal, Montréal, QC, CanadaIntroductionThe use of antiretroviral therapy (ART) during pregnancy, particularly protease-inhibitor-based regimens (PI), has been linked to adverse outcomes including preterm delivery. As this outcome may be related to systemic inflammation, we sought to characterize inflammatory profiles of pregnant people living with HIV (PLWH) by comparing their levels of inflammatory mediators at two timepoints during pregnancy according to ART regimen, and to HIV-negative controls.MethodsSecond and third trimester samples from 144 pregnant PLWH treated with ART and 24 HIV-uninfected controls were retrieved from the CARMA-PREG cohort. Peripheral plasma levels of 12 inflammatory mediators previously linked to HIV infection and/or poor pregnancy outcomes were quantified by multiplex assay: HMGB1, GM-CSF, IFNα, IFNβ, IFNγ, IL-10, IL-17, IL-1β, IL-6, TNFα, AGP, and CRP. Levels were compared by ART regimen and HIV status.ResultsAdjusted analyses showed that PLWH have higher levels of AGP throughout pregnancy and lower levels of IFNγ and IL-1β during the second trimester. PI-based regimens are associated with significantly higher levels of IFNα and IL-17 during the second trimester and IFNα, CRP, HMGB1, and IFNβ during the third trimester compared to InSTI-based regimens. The PI-subgroup was associated with preterm delivery and higher HIV-1 viral load.DiscussionOur results suggest that PI-based regimens are associated with a pro-inflammatory and antiviral immunological response and a high viral load, which may be a mechanism through which PI-based regimens increase the risk of preterm delivery. Further investigations into cellular mechanisms and pro-inflammatory cascades leading to preterm delivery are necessary to support this association.https://www.frontiersin.org/articles/10.3389/fmicb.2023.1282291/fullHIVantiretroviral therapypregnancyinflammationpremature birth |
spellingShingle | Stephanie Hindle Stephanie Hindle Sylvie Girard Sylvie Girard Sylvie Girard Sylvie Girard Helene C. F. Cote Helene C. F. Cote Helene C. F. Cote Deborah Money Deborah Money Evelyn Mann Evelyn Mann Isabelle Boucoiran Isabelle Boucoiran Isabelle Boucoiran for the Children and Women Antiretroviral Therapy and Makers of Aging (Carma) Preg Team Circulating levels of inflammatory mediators in pregnant people living with HIV according to antiretroviral therapy regimen Frontiers in Microbiology HIV antiretroviral therapy pregnancy inflammation premature birth |
title | Circulating levels of inflammatory mediators in pregnant people living with HIV according to antiretroviral therapy regimen |
title_full | Circulating levels of inflammatory mediators in pregnant people living with HIV according to antiretroviral therapy regimen |
title_fullStr | Circulating levels of inflammatory mediators in pregnant people living with HIV according to antiretroviral therapy regimen |
title_full_unstemmed | Circulating levels of inflammatory mediators in pregnant people living with HIV according to antiretroviral therapy regimen |
title_short | Circulating levels of inflammatory mediators in pregnant people living with HIV according to antiretroviral therapy regimen |
title_sort | circulating levels of inflammatory mediators in pregnant people living with hiv according to antiretroviral therapy regimen |
topic | HIV antiretroviral therapy pregnancy inflammation premature birth |
url | https://www.frontiersin.org/articles/10.3389/fmicb.2023.1282291/full |
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