Dissecting drivers of immune activation in chronic HIV-1 infection.

Anti-HIV Agents / therapeutic use Cohort Studies Female HIV Infections HIV-1 Humans Male Viremia / drug therapy
Antiretroviral therapy HIV Immune activation Inflammation

Journal

EBioMedicine
ISSN: 2352-3964
Titre abrégé: EBioMedicine
Pays: Netherlands
ID NLM: 101647039

Informations de publication

Date de publication:
Sep 2022
Historique:
received: 06 01 2022
revised: 22 05 2022
accepted: 05 07 2022
pubmed: 30 7 2022
medline: 21 9 2022
entrez: 29 7 2022
Statut: ppublish

Résumé

Immune activation is a significant contributor to HIV pathogenesis and disease progression. In virally-suppressed individuals on ART, low-level immune activation has been linked to several non-infectious comorbid diseases. However, studies have not been systematically performed in sub-Saharan Africa and thus the impact of demographics, ART and regional endemic co-infections on immune activation is not known. We therefore comprehensively evaluated in a large multinational African cohort markers for immune activation and its distribution in various settings. 2747 specimens from 2240 people living with HIV (PLWH) and 477 without HIV from the observational African Cohort Study (AFRICOS) were analyzed for 13 immune parameters. Samples were collected along with medical history, sociodemographic and comorbidity data at 12 HIV clinics across 5 programs in Uganda, Kenya, Tanzania and Nigeria. Data were analyzed with univariate and multivariate methods such as random forests and principal component analysis. Immune activation was markedly different between PLWH with detectable viral loads, and individuals without HIV across sites. Among viremic PLWH, we found that all immune parameters were significantly correlated with viral load except for IFN-α. The overall inflammatory profile was distinct between men and women living with HIV, in individuals off ART and with HIV viremia. We observed stronger differences in the immune activation profile with increasing viremia. Using machine learning methods, we found that geographic differences contributed to unique inflammatory profiles. We also found that among PLWH, age and the presence of infectious and/or noninfectious comorbidities showed distinct inflammatory patterns, and biomarkers may be used to predict the presence of some comorbidities. Our findings show that chronic immune activation in HIV-1 infection is influenced by HIV viral load, sex, age, region and ART use. These predictors, as well as associations among some biomarkers and coinfections, influence biomarkers associated with noncommunicable diseases. This work was supported by the President's Emergency Plan for AIDS Relief via a cooperative agreement between the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., and the U.S. Department of Defense [W81XWH-11-2-0174, W81XWH-18-2-0040]. The investigators have adhered to the policies for protection of human subjects as prescribed in AR 70-25. This article was prepared while Michael A. Eller was employed at Henry M. Jackson Foundation for the Advancement of Military Medicine for the U.S. Military HIV Research Program. The views expressed are those of the authors and should not be construed to represent the positions of the US Army or the Department of Defense. The opinions expressed in this article are the author's own, and do not reflect the view of the National Institutes of Health, the U.S. Department of Health and Human Services, or the U.S. government.

Sections du résumé

BACKGROUND BACKGROUND
Immune activation is a significant contributor to HIV pathogenesis and disease progression. In virally-suppressed individuals on ART, low-level immune activation has been linked to several non-infectious comorbid diseases. However, studies have not been systematically performed in sub-Saharan Africa and thus the impact of demographics, ART and regional endemic co-infections on immune activation is not known. We therefore comprehensively evaluated in a large multinational African cohort markers for immune activation and its distribution in various settings.
METHODS METHODS
2747 specimens from 2240 people living with HIV (PLWH) and 477 without HIV from the observational African Cohort Study (AFRICOS) were analyzed for 13 immune parameters. Samples were collected along with medical history, sociodemographic and comorbidity data at 12 HIV clinics across 5 programs in Uganda, Kenya, Tanzania and Nigeria. Data were analyzed with univariate and multivariate methods such as random forests and principal component analysis.
FINDINGS RESULTS
Immune activation was markedly different between PLWH with detectable viral loads, and individuals without HIV across sites. Among viremic PLWH, we found that all immune parameters were significantly correlated with viral load except for IFN-α. The overall inflammatory profile was distinct between men and women living with HIV, in individuals off ART and with HIV viremia. We observed stronger differences in the immune activation profile with increasing viremia. Using machine learning methods, we found that geographic differences contributed to unique inflammatory profiles. We also found that among PLWH, age and the presence of infectious and/or noninfectious comorbidities showed distinct inflammatory patterns, and biomarkers may be used to predict the presence of some comorbidities.
INTERPRETATION CONCLUSIONS
Our findings show that chronic immune activation in HIV-1 infection is influenced by HIV viral load, sex, age, region and ART use. These predictors, as well as associations among some biomarkers and coinfections, influence biomarkers associated with noncommunicable diseases.
FUNDING BACKGROUND
This work was supported by the President's Emergency Plan for AIDS Relief via a cooperative agreement between the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., and the U.S. Department of Defense [W81XWH-11-2-0174, W81XWH-18-2-0040]. The investigators have adhered to the policies for protection of human subjects as prescribed in AR 70-25. This article was prepared while Michael A. Eller was employed at Henry M. Jackson Foundation for the Advancement of Military Medicine for the U.S. Military HIV Research Program. The views expressed are those of the authors and should not be construed to represent the positions of the US Army or the Department of Defense. The opinions expressed in this article are the author's own, and do not reflect the view of the National Institutes of Health, the U.S. Department of Health and Human Services, or the U.S. government.

Identifiants

DOI: 10.1016/j.ebiom.2022.104182 PMID: 35905559 PMC: PMC9334338
pubmed: 35905559
pii: S2352-3964(22)00363-2
doi: 10.1016/j.ebiom.2022.104182
pmc: PMC9334338
pii:
doi:

Substances chimiques

Anti-HIV Agents 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

104182

Informations de copyright

Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests All authors declare no conflicts of interest.

Auteurs

Hendrik Streeck (H)

Institute of Virology, Medical Faculty, University Bonn, Bonn, Germany; German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, 53127 Bonn, Germany. Electronic address: hendrik.streeck@ukbonn.de.

Alvino Maestri (A)

Institute for HIV Research, University Hospital, University Duisburg-Essen, Essen, Germany.

Daniel Habermann (D)

Bioinformatics and Computational Biophysics, University Duisburg-Essen, Essen, Germany.

Trevor A Crowell (TA)

U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., Bethesda, MD, USA.

Allahna L Esber (AL)

U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., Bethesda, MD, USA.

Gowoon Son (G)

Institute for HIV Research, University Hospital, University Duisburg-Essen, Essen, Germany.

Leigh Anne Eller (LA)

U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., Bethesda, MD, USA.

Michael A Eller (MA)

U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., Bethesda, MD, USA; Vaccine Research Program, DAIDS, NIAID, NIH, Bethesda, MD, USA.

Ajay P Parikh (AP)

U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., Bethesda, MD, USA.

Peter A Horn (PA)

Institute for Transfusion Medicine, University Hospital, University Duisburg-Essen, Essen, Germany.

Lucas Maganga (L)

U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA; National Institute for Medical Research-Mbeya Medical Research Center, Mbeya, Tanzania.

Emmanuel Bahemana (E)

U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA; HJF Medical Research International, Mbeya, Tanzania.

Yakubu Adamu (Y)

U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA; U.S. Army Medical Research Directorate - Africa, Abuja, Nigeria.

Francis Kiweewa (F)

Makerere University Walter Reed Project, Kampala, Uganda.

Jonah Maswai (J)

U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA; HJF Medical Research International, Kericho, Kenya.

John Owuoth (J)

U.S. Army Medical Research Directorate - Africa, Kisumu, Kenya; HJF Medical Research International, Kisumu, Kenya.

Merlin L Robb (ML)

U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., Bethesda, MD, USA.

Nelson L Michael (NL)

U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Christina S Polyak (CS)

U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., Bethesda, MD, USA.

Daniel Hoffmann (D)

Bioinformatics and Computational Biophysics, University Duisburg-Essen, Essen, Germany.

Julie A Ake (JA)

U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

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Classifications MeSH

questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Anti-infectieux › Antiviraux › Antirétroviraux › Agents antiVIH › Dissecting drivers of immune activation in...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études de cohortes › Dissecting drivers of immune activation in...
questionsmedicales.fr › Maladies du système immunitaire › Déficits immunitaires › Infections à VIH › Dissecting drivers of immune activation in...
questionsmedicales.fr › Virus › Virus à ARN › Retroviridae › Lentivirus › Lentivirus des primates › VIH (Virus de l'Immunodéficience Humaine) › VIH-1 (Virus de l'Immunodéficience Humaine de type 1) › Dissecting drivers of immune activation in...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Dissecting drivers of immune activation in...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Inflammation › Sepsie › Virémie › Dissecting drivers of immune activation in...