Are plasma biomarkers of immune activation predictive of HIV progression: a longitudinal comparison and analyses in HIV-1 and HIV-2 infections?

<h4>Background</h4>Chronic immune activation is a hallmark of HIV infection and has been associated with disease progression. Assessment of soluble biomarkers indicating immune activation provide clues into pathogenesis and hold promise for the development of point-of-care monitoring of...

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Main Authors: Samuel Nyamweya, John Townend, Akram Zaman, Sarah Jane Steele, David Jeffries, Sarah Rowland-Jones, Hilton Whittle, Katie L Flanagan, Assan Jaye
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2012-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0044411&type=printable
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author Samuel Nyamweya
John Townend
Akram Zaman
Sarah Jane Steele
David Jeffries
Sarah Rowland-Jones
Hilton Whittle
Katie L Flanagan
Assan Jaye
author_facet Samuel Nyamweya
John Townend
Akram Zaman
Sarah Jane Steele
David Jeffries
Sarah Rowland-Jones
Hilton Whittle
Katie L Flanagan
Assan Jaye
author_sort Samuel Nyamweya
collection DOAJ
description <h4>Background</h4>Chronic immune activation is a hallmark of HIV infection and has been associated with disease progression. Assessment of soluble biomarkers indicating immune activation provide clues into pathogenesis and hold promise for the development of point-of-care monitoring of HIV in resource-poor-settings. Their evaluation in cohort resources is therefore needed to further their development and use in HIV research.<h4>Methodology/principal findings</h4>Longitudinal evaluation of βeta-2 microglobulin (β-2 m), neopterin and suPAR soluble urokinase-type plasminogen activator receptor (suPAR) was performed with archived plasma samples to predict disease progression and provided the first direct comparison of levels in HIV-1 and HIV-2 infections. At least 2095 samples from 137 HIV-1 and 198 HIV-2 subjects with starting CD4% of ≥ 28 and median follow up of 4 years were analysed. All biomarkers were correlated negatively to CD4% and positively to viral load and to each other. Analyses in subjects living for ≥ 5 years revealed increases in median β-2 m and neopterin and decreases in CD4% over this period and the odds of death within 5 years were positively associated with baseline levels of β-2 m and neopterin. ROC analyses strengthened the evidence of elevation of biomarkers in patients approaching death in both HIV-1 and HIV-2 infections. Regression models showed that rates of biomarker fold change accelerated from 6-8 years before death with no significant differences between biomarker levels in HIV-1 and HIV-2 at equal time points prior to death.An 'immune activation index' analysis indicative of biomarker levels at equivalent viral loads also showed no differences between the two infections.<h4>Conclusions/significance</h4>Our results suggest that β-2 m and neopterin are useful tools for disease monitoring in both HIV-1 and HIV-2 infections, whereas sUPAR performed less well. Levels of immune activation per amount of virus were comparable in HIV-1 and HIV-2 infected subjects.
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spelling doaj-art-b41ca0e61f4e4ba19788c4a1e79f40112025-08-20T03:10:18ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0179e4441110.1371/journal.pone.0044411Are plasma biomarkers of immune activation predictive of HIV progression: a longitudinal comparison and analyses in HIV-1 and HIV-2 infections?Samuel NyamweyaJohn TownendAkram ZamanSarah Jane SteeleDavid JeffriesSarah Rowland-JonesHilton WhittleKatie L FlanaganAssan Jaye<h4>Background</h4>Chronic immune activation is a hallmark of HIV infection and has been associated with disease progression. Assessment of soluble biomarkers indicating immune activation provide clues into pathogenesis and hold promise for the development of point-of-care monitoring of HIV in resource-poor-settings. Their evaluation in cohort resources is therefore needed to further their development and use in HIV research.<h4>Methodology/principal findings</h4>Longitudinal evaluation of βeta-2 microglobulin (β-2 m), neopterin and suPAR soluble urokinase-type plasminogen activator receptor (suPAR) was performed with archived plasma samples to predict disease progression and provided the first direct comparison of levels in HIV-1 and HIV-2 infections. At least 2095 samples from 137 HIV-1 and 198 HIV-2 subjects with starting CD4% of ≥ 28 and median follow up of 4 years were analysed. All biomarkers were correlated negatively to CD4% and positively to viral load and to each other. Analyses in subjects living for ≥ 5 years revealed increases in median β-2 m and neopterin and decreases in CD4% over this period and the odds of death within 5 years were positively associated with baseline levels of β-2 m and neopterin. ROC analyses strengthened the evidence of elevation of biomarkers in patients approaching death in both HIV-1 and HIV-2 infections. Regression models showed that rates of biomarker fold change accelerated from 6-8 years before death with no significant differences between biomarker levels in HIV-1 and HIV-2 at equal time points prior to death.An 'immune activation index' analysis indicative of biomarker levels at equivalent viral loads also showed no differences between the two infections.<h4>Conclusions/significance</h4>Our results suggest that β-2 m and neopterin are useful tools for disease monitoring in both HIV-1 and HIV-2 infections, whereas sUPAR performed less well. Levels of immune activation per amount of virus were comparable in HIV-1 and HIV-2 infected subjects.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0044411&type=printable
spellingShingle Samuel Nyamweya
John Townend
Akram Zaman
Sarah Jane Steele
David Jeffries
Sarah Rowland-Jones
Hilton Whittle
Katie L Flanagan
Assan Jaye
Are plasma biomarkers of immune activation predictive of HIV progression: a longitudinal comparison and analyses in HIV-1 and HIV-2 infections?
PLoS ONE
title Are plasma biomarkers of immune activation predictive of HIV progression: a longitudinal comparison and analyses in HIV-1 and HIV-2 infections?
title_full Are plasma biomarkers of immune activation predictive of HIV progression: a longitudinal comparison and analyses in HIV-1 and HIV-2 infections?
title_fullStr Are plasma biomarkers of immune activation predictive of HIV progression: a longitudinal comparison and analyses in HIV-1 and HIV-2 infections?
title_full_unstemmed Are plasma biomarkers of immune activation predictive of HIV progression: a longitudinal comparison and analyses in HIV-1 and HIV-2 infections?
title_short Are plasma biomarkers of immune activation predictive of HIV progression: a longitudinal comparison and analyses in HIV-1 and HIV-2 infections?
title_sort are plasma biomarkers of immune activation predictive of hiv progression a longitudinal comparison and analyses in hiv 1 and hiv 2 infections
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0044411&type=printable
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