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Plasma calprotectin as a biomarker of mortality at antiretroviral treatment initiation in advanced HIV – pilot study

Background: In advanced HIV, significant mortality occurs soon after starting antiretroviral treatment (ART) in low- and middle-incomes countries. Calprotectin is a biomarker of innate response to infection and inflammatory conditions. We examined the association between plasma calprotectin collecte...

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Autores principales: Kamau, Faith W., Gwela, Agnes, Nyerere, Andrew K., Riitho, Victor, Njunge, James M., Ngari, Moses M., Prendergast, Andrew J., Berkley, James A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: F1000 Research Limited 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7722532/
https://www.ncbi.nlm.nih.gov/pubmed/33336080
http://dx.doi.org/10.12688/wellcomeopenres.15563.2
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author Kamau, Faith W.
Gwela, Agnes
Nyerere, Andrew K.
Riitho, Victor
Njunge, James M.
Ngari, Moses M.
Prendergast, Andrew J.
Berkley, James A.
author_facet Kamau, Faith W.
Gwela, Agnes
Nyerere, Andrew K.
Riitho, Victor
Njunge, James M.
Ngari, Moses M.
Prendergast, Andrew J.
Berkley, James A.
author_sort Kamau, Faith W.
collection PubMed
description Background: In advanced HIV, significant mortality occurs soon after starting antiretroviral treatment (ART) in low- and middle-incomes countries. Calprotectin is a biomarker of innate response to infection and inflammatory conditions. We examined the association between plasma calprotectin collected before ART treatment and mortality among individuals with advanced HIV.   Methods: We conducted a pilot case-cohort study among HIV infected adults and adolescents over 13 years old with CD4+ <100/mm3 at ART initiation at two Kenyan sites. Participants received three factorial randomised interventions in addition to ART within the REALITY trial (ISRCTN43622374). Calprotectin collected at baseline (before ART) and after 4 weeks of treatment was measured in archived plasma of those who died within 24 weeks (cases) and randomly selected participants who survived (non-cases). Association with mortality was assessed using Cox proportional hazards models with inverse sampling probability weights and adjusted for age, sex, site, BMI, viral load, randomised treatments, and clustered by CD4+ count (0-24, 25-49, and 50-99 cells/mm3).   Results: Baseline median (IQR) plasma calprotectin was 6.82 (2.65–12.5) µg/ml in cases (n=39) and 5.01 (1.92–11.5) µg/ml in non-cases (n=58). Baseline calprotectin was associated with age, neutrophil count and the presence of cough, but not other measured indicators of infection. In adjusted multivariable models, baseline calprotectin was associated with subsequent mortality: HR 1.64 (95% CI 1.11 - 2.42) and HR 2.77 (95% CI 1.58 - 4.88) for deaths during the first twenty-four and four weeks respectively. Calprotectin levels fell between baseline and 4 weeks among both cases and non-cases irrespective of randomised interventions.   Conclusions: Among individuals with advanced HIV starting ART in Kenya, plasma calprotectin may have potential as a biomarker of early mortality. Validation in larger studies, comparison with other biomarkers and investigation of the sources of infection and inflammation are warranted.
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spelling pubmed-77225322020-12-16 Plasma calprotectin as a biomarker of mortality at antiretroviral treatment initiation in advanced HIV – pilot study Kamau, Faith W. Gwela, Agnes Nyerere, Andrew K. Riitho, Victor Njunge, James M. Ngari, Moses M. Prendergast, Andrew J. Berkley, James A. Wellcome Open Res Research Article Background: In advanced HIV, significant mortality occurs soon after starting antiretroviral treatment (ART) in low- and middle-incomes countries. Calprotectin is a biomarker of innate response to infection and inflammatory conditions. We examined the association between plasma calprotectin collected before ART treatment and mortality among individuals with advanced HIV.   Methods: We conducted a pilot case-cohort study among HIV infected adults and adolescents over 13 years old with CD4+ <100/mm3 at ART initiation at two Kenyan sites. Participants received three factorial randomised interventions in addition to ART within the REALITY trial (ISRCTN43622374). Calprotectin collected at baseline (before ART) and after 4 weeks of treatment was measured in archived plasma of those who died within 24 weeks (cases) and randomly selected participants who survived (non-cases). Association with mortality was assessed using Cox proportional hazards models with inverse sampling probability weights and adjusted for age, sex, site, BMI, viral load, randomised treatments, and clustered by CD4+ count (0-24, 25-49, and 50-99 cells/mm3).   Results: Baseline median (IQR) plasma calprotectin was 6.82 (2.65–12.5) µg/ml in cases (n=39) and 5.01 (1.92–11.5) µg/ml in non-cases (n=58). Baseline calprotectin was associated with age, neutrophil count and the presence of cough, but not other measured indicators of infection. In adjusted multivariable models, baseline calprotectin was associated with subsequent mortality: HR 1.64 (95% CI 1.11 - 2.42) and HR 2.77 (95% CI 1.58 - 4.88) for deaths during the first twenty-four and four weeks respectively. Calprotectin levels fell between baseline and 4 weeks among both cases and non-cases irrespective of randomised interventions.   Conclusions: Among individuals with advanced HIV starting ART in Kenya, plasma calprotectin may have potential as a biomarker of early mortality. Validation in larger studies, comparison with other biomarkers and investigation of the sources of infection and inflammation are warranted. F1000 Research Limited 2020-11-27 /pmc/articles/PMC7722532/ /pubmed/33336080 http://dx.doi.org/10.12688/wellcomeopenres.15563.2 Text en Copyright: © 2020 Kamau FW et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Kamau, Faith W.
Gwela, Agnes
Nyerere, Andrew K.
Riitho, Victor
Njunge, James M.
Ngari, Moses M.
Prendergast, Andrew J.
Berkley, James A.
Plasma calprotectin as a biomarker of mortality at antiretroviral treatment initiation in advanced HIV – pilot study
title Plasma calprotectin as a biomarker of mortality at antiretroviral treatment initiation in advanced HIV – pilot study
title_full Plasma calprotectin as a biomarker of mortality at antiretroviral treatment initiation in advanced HIV – pilot study
title_fullStr Plasma calprotectin as a biomarker of mortality at antiretroviral treatment initiation in advanced HIV – pilot study
title_full_unstemmed Plasma calprotectin as a biomarker of mortality at antiretroviral treatment initiation in advanced HIV – pilot study
title_short Plasma calprotectin as a biomarker of mortality at antiretroviral treatment initiation in advanced HIV – pilot study
title_sort plasma calprotectin as a biomarker of mortality at antiretroviral treatment initiation in advanced hiv – pilot study
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7722532/
https://www.ncbi.nlm.nih.gov/pubmed/33336080
http://dx.doi.org/10.12688/wellcomeopenres.15563.2
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