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Effect of the relationship between anaemia and systemic inflammation on the risk of incident tuberculosis and death in people with advanced HIV: a sub-analysis of the REMEMBER trial

BACKGROUND: Tuberculosis (TB) is an infectious morbidity that commonly occurs in people living with HIV (PWH) and increases the progression of HIV disease, as well as the risk of death. Simple markers of progression are much needed to identify those at highest risk for poor outcome. This study aimed...

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Autores principales: Araújo-Pereira, Mariana, Krishnan, Sonya, Salgame, Padmini, Manabe, Yukari C., Hosseinipour, Mina C., Bisson, Gregory, Severe, Damocles Patrice, Rouzier, Vanessa, Leong, Samantha, Mave, Vidya, Sawe, Fredrick Kipyego, Siika, Abraham M., Kanyama, Cecilia, Dadabhai, Sufia S., Lama, Javier R., Valencia-Huamani, Javier, Badal-Faesen, Sharlaa, Lalloo, Umesh Gangaram, Naidoo, Kogieleum, Mohapi, Lerato, Kityo, Cissy, Andrade, Bruno B., Gupta, Amita
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10242630/
https://www.ncbi.nlm.nih.gov/pubmed/37287871
http://dx.doi.org/10.1016/j.eclinm.2023.102030
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author Araújo-Pereira, Mariana
Krishnan, Sonya
Salgame, Padmini
Manabe, Yukari C.
Hosseinipour, Mina C.
Bisson, Gregory
Severe, Damocles Patrice
Rouzier, Vanessa
Leong, Samantha
Mave, Vidya
Sawe, Fredrick Kipyego
Siika, Abraham M.
Kanyama, Cecilia
Dadabhai, Sufia S.
Lama, Javier R.
Valencia-Huamani, Javier
Badal-Faesen, Sharlaa
Lalloo, Umesh Gangaram
Naidoo, Kogieleum
Mohapi, Lerato
Kityo, Cissy
Andrade, Bruno B.
Gupta, Amita
author_facet Araújo-Pereira, Mariana
Krishnan, Sonya
Salgame, Padmini
Manabe, Yukari C.
Hosseinipour, Mina C.
Bisson, Gregory
Severe, Damocles Patrice
Rouzier, Vanessa
Leong, Samantha
Mave, Vidya
Sawe, Fredrick Kipyego
Siika, Abraham M.
Kanyama, Cecilia
Dadabhai, Sufia S.
Lama, Javier R.
Valencia-Huamani, Javier
Badal-Faesen, Sharlaa
Lalloo, Umesh Gangaram
Naidoo, Kogieleum
Mohapi, Lerato
Kityo, Cissy
Andrade, Bruno B.
Gupta, Amita
author_sort Araújo-Pereira, Mariana
collection PubMed
description BACKGROUND: Tuberculosis (TB) is an infectious morbidity that commonly occurs in people living with HIV (PWH) and increases the progression of HIV disease, as well as the risk of death. Simple markers of progression are much needed to identify those at highest risk for poor outcome. This study aimed to assess how baseline severity of anaemia and associated inflammatory profiles impact death and the incidence of TB in a cohort of PWH who received TB preventive therapy (TPT). METHODS: This study is a secondary posthoc analysis of the AIDS Clinical Trials Group A5274 REMEMBER clinical trial (NCT0138008), an open-label randomised clinical trial of antiretroviral-naïve PWH with CD4 <50 cells/μL, performed from October 31, 2011 to June 9, 2014, from 18 outpatient research clinics in 10 low- and middle-income countries (Malawi, South Africa, Haiti, Kenya, Zambia, India, Brazil, Zimbabwe, Peru, and Uganda) who initiated antiretroviral therapy and either isoniazid TPT or 4-drug empiric TB therapy. Plasma concentrations of several soluble inflammatory biomarkers were measured prior to the commencement of antiretroviral and anti-TB therapies, and participants were followed up for at least 48 weeks. Incident TB or death during this period were primary outcomes. We performed multidimensional analyses, logistic regression analyses, survival curves, and Bayesian network analyses to delineate associations between anaemia, laboratory parameters, and clinical outcomes. FINDINGS: Of all 269 participants, 76.2% (n = 205) were anaemic, and 31.2% (n = 84) had severe anaemia. PWH with moderate/severe anaemia exhibited a pronounced systemic pro-inflammatory profile compared to those with mild or without anaemia, hallmarked by a substantial increase in IL-6 plasma concentrations. Moderate/severe anaemia was also associated with incident TB incidence (aOR: 3.59, 95% CI: 1.32–9.76, p = 0.012) and death (aOR: 3.63, 95% CI: 1.07–12.33, p = 0.039). INTERPRETATION: Our findings suggest that PWH with moderate/severe anaemia display a distinct pro-inflammatory profile. The presence of moderate/severe anaemia pre-ART was independently associated with the development of TB and death. PWH with anaemia should be monitored closely to minimise the occurrence of unfavourable outcomes. FUNDING: 10.13039/100000002National Institutes of Health.
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spelling pubmed-102426302023-06-07 Effect of the relationship between anaemia and systemic inflammation on the risk of incident tuberculosis and death in people with advanced HIV: a sub-analysis of the REMEMBER trial Araújo-Pereira, Mariana Krishnan, Sonya Salgame, Padmini Manabe, Yukari C. Hosseinipour, Mina C. Bisson, Gregory Severe, Damocles Patrice Rouzier, Vanessa Leong, Samantha Mave, Vidya Sawe, Fredrick Kipyego Siika, Abraham M. Kanyama, Cecilia Dadabhai, Sufia S. Lama, Javier R. Valencia-Huamani, Javier Badal-Faesen, Sharlaa Lalloo, Umesh Gangaram Naidoo, Kogieleum Mohapi, Lerato Kityo, Cissy Andrade, Bruno B. Gupta, Amita eClinicalMedicine Articles BACKGROUND: Tuberculosis (TB) is an infectious morbidity that commonly occurs in people living with HIV (PWH) and increases the progression of HIV disease, as well as the risk of death. Simple markers of progression are much needed to identify those at highest risk for poor outcome. This study aimed to assess how baseline severity of anaemia and associated inflammatory profiles impact death and the incidence of TB in a cohort of PWH who received TB preventive therapy (TPT). METHODS: This study is a secondary posthoc analysis of the AIDS Clinical Trials Group A5274 REMEMBER clinical trial (NCT0138008), an open-label randomised clinical trial of antiretroviral-naïve PWH with CD4 <50 cells/μL, performed from October 31, 2011 to June 9, 2014, from 18 outpatient research clinics in 10 low- and middle-income countries (Malawi, South Africa, Haiti, Kenya, Zambia, India, Brazil, Zimbabwe, Peru, and Uganda) who initiated antiretroviral therapy and either isoniazid TPT or 4-drug empiric TB therapy. Plasma concentrations of several soluble inflammatory biomarkers were measured prior to the commencement of antiretroviral and anti-TB therapies, and participants were followed up for at least 48 weeks. Incident TB or death during this period were primary outcomes. We performed multidimensional analyses, logistic regression analyses, survival curves, and Bayesian network analyses to delineate associations between anaemia, laboratory parameters, and clinical outcomes. FINDINGS: Of all 269 participants, 76.2% (n = 205) were anaemic, and 31.2% (n = 84) had severe anaemia. PWH with moderate/severe anaemia exhibited a pronounced systemic pro-inflammatory profile compared to those with mild or without anaemia, hallmarked by a substantial increase in IL-6 plasma concentrations. Moderate/severe anaemia was also associated with incident TB incidence (aOR: 3.59, 95% CI: 1.32–9.76, p = 0.012) and death (aOR: 3.63, 95% CI: 1.07–12.33, p = 0.039). INTERPRETATION: Our findings suggest that PWH with moderate/severe anaemia display a distinct pro-inflammatory profile. The presence of moderate/severe anaemia pre-ART was independently associated with the development of TB and death. PWH with anaemia should be monitored closely to minimise the occurrence of unfavourable outcomes. FUNDING: 10.13039/100000002National Institutes of Health. Elsevier 2023-06-02 /pmc/articles/PMC10242630/ /pubmed/37287871 http://dx.doi.org/10.1016/j.eclinm.2023.102030 Text en © 2023 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Articles
Araújo-Pereira, Mariana
Krishnan, Sonya
Salgame, Padmini
Manabe, Yukari C.
Hosseinipour, Mina C.
Bisson, Gregory
Severe, Damocles Patrice
Rouzier, Vanessa
Leong, Samantha
Mave, Vidya
Sawe, Fredrick Kipyego
Siika, Abraham M.
Kanyama, Cecilia
Dadabhai, Sufia S.
Lama, Javier R.
Valencia-Huamani, Javier
Badal-Faesen, Sharlaa
Lalloo, Umesh Gangaram
Naidoo, Kogieleum
Mohapi, Lerato
Kityo, Cissy
Andrade, Bruno B.
Gupta, Amita
Effect of the relationship between anaemia and systemic inflammation on the risk of incident tuberculosis and death in people with advanced HIV: a sub-analysis of the REMEMBER trial
title Effect of the relationship between anaemia and systemic inflammation on the risk of incident tuberculosis and death in people with advanced HIV: a sub-analysis of the REMEMBER trial
title_full Effect of the relationship between anaemia and systemic inflammation on the risk of incident tuberculosis and death in people with advanced HIV: a sub-analysis of the REMEMBER trial
title_fullStr Effect of the relationship between anaemia and systemic inflammation on the risk of incident tuberculosis and death in people with advanced HIV: a sub-analysis of the REMEMBER trial
title_full_unstemmed Effect of the relationship between anaemia and systemic inflammation on the risk of incident tuberculosis and death in people with advanced HIV: a sub-analysis of the REMEMBER trial
title_short Effect of the relationship between anaemia and systemic inflammation on the risk of incident tuberculosis and death in people with advanced HIV: a sub-analysis of the REMEMBER trial
title_sort effect of the relationship between anaemia and systemic inflammation on the risk of incident tuberculosis and death in people with advanced hiv: a sub-analysis of the remember trial
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10242630/
https://www.ncbi.nlm.nih.gov/pubmed/37287871
http://dx.doi.org/10.1016/j.eclinm.2023.102030
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