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https://www.arca.fiocruz.br/handle/icict/61571
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
Hemoglobina
Inflamação sistêmica
HIV
Incidente TB
Anemia
Inflamação
Morte
Author
Pereira, Mariana Araújo
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.
Huamani, Javier Valencia
Badal-Faesen, Sharlaa
Lalloo, Umesh Gangaram
Naidoo, Kogieleum
Mohapi, Lerato
Kityo, Cissy
Andrade, Bruno B.
Guptae, Amita
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.
Huamani, Javier Valencia
Badal-Faesen, Sharlaa
Lalloo, Umesh Gangaram
Naidoo, Kogieleum
Mohapi, Lerato
Kityo, Cissy
Andrade, Bruno B.
Guptae, Amita
Affilliation
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative. Salvador, BA, Brasil / Universidade Federal da Bahia. Programa de Pós-Graduação em Patologia Humana e Experimental. Salvador, BA, Brasil / Faculdade de Tecnologia e Ciências. Curso de Medicina. Salvador, BA, Brasil.
Department of Medicine. Johns Hopkins University School of Medicine. Baltimore, MD, USA.
Department of Medicine. Rutgers New Jersey Medical School. Newark, USA.
Department of Medicine. Johns Hopkins University School of Medicine. Baltimore, MD, USA.
Department of Medicine. University of North Carolina at Chapel Hill. Chapel Hill, NC, USA.
University of Pennsylvania Perelman School of Medicine. Philadelphia, PA, USA.
Les Centres Haitian Group for the Study of Kaposi’s Sarcoma and Opportunistic Infections (GHESKIO). Port-au-Prince, Haiti.
Les Centres Haitian Group for the Study of Kaposi’s Sarcoma and Opportunistic Infections (GHESKIO). Port-au-Prince, Haiti.
Department of Medicine. Rutgers New Jersey Medical School. Newark, USA.
BJ Medical College Clinical Research Site. Pune, India.
Henry M. Jackson Foundation for the Advancement of Military Medicine. Bethesda, MD, USA.
Department of Medicine. School of Medicine. Moi University. Eldoret, Kenya.
University of North Carolina Project. Kamazu Central Hospital. Lilongwe, Malawi
Johns Hopkins Bloomberg School of Public Health. Blantyre, Malawi.
Asociacion Civil Impacta Salud y Educacion. Lima, Peru.
Asociacion Civil Impacta Salud y Educacion. Lima, Peru.
Clinical HIV Research Unit. School of Clinical Medicine. University of Witwatersrand, Johannesburg, South Africa.
Morningside Mediclinic. Sandton, Johannesburg, South Africa.
Centre for the AIDS Programme of Research in South Africa (CAPRISA). University of KwaZulu-Natal Nelson R Mandela School of Medicine. Durban, South Africa / SA-Medical Research Council (MRC)-CAPRISA-HIV-TB Pathogenesis and Treatment Research Unit. University of KwaZulu-Natal Nelson R Mandela School of Medicine. Durban, South Africa.
School of Clinical Medicine. University of Witwatersrand. Johannesburg. South Africa
HIV Medicine. Joint Clinical Research Centre. Kampala, Uganda.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative. Salvador, BA, Brasil / Universidade Federal da Bahia. Programa de Pós-Graduação em Patologia Humana e Experimental. Salvador, BA, Brasil / Faculdade de Tecnologia e Ciências. Curso de Medicina. Salvador, BA, Brasil.
Department of Medicine. Johns Hopkins University School of Medicine. Baltimore, MD, USA.
Department of Medicine. Johns Hopkins University School of Medicine. Baltimore, MD, USA.
Department of Medicine. Rutgers New Jersey Medical School. Newark, USA.
Department of Medicine. Johns Hopkins University School of Medicine. Baltimore, MD, USA.
Department of Medicine. University of North Carolina at Chapel Hill. Chapel Hill, NC, USA.
University of Pennsylvania Perelman School of Medicine. Philadelphia, PA, USA.
Les Centres Haitian Group for the Study of Kaposi’s Sarcoma and Opportunistic Infections (GHESKIO). Port-au-Prince, Haiti.
Les Centres Haitian Group for the Study of Kaposi’s Sarcoma and Opportunistic Infections (GHESKIO). Port-au-Prince, Haiti.
Department of Medicine. Rutgers New Jersey Medical School. Newark, USA.
BJ Medical College Clinical Research Site. Pune, India.
Henry M. Jackson Foundation for the Advancement of Military Medicine. Bethesda, MD, USA.
Department of Medicine. School of Medicine. Moi University. Eldoret, Kenya.
University of North Carolina Project. Kamazu Central Hospital. Lilongwe, Malawi
Johns Hopkins Bloomberg School of Public Health. Blantyre, Malawi.
Asociacion Civil Impacta Salud y Educacion. Lima, Peru.
Asociacion Civil Impacta Salud y Educacion. Lima, Peru.
Clinical HIV Research Unit. School of Clinical Medicine. University of Witwatersrand, Johannesburg, South Africa.
Morningside Mediclinic. Sandton, Johannesburg, South Africa.
Centre for the AIDS Programme of Research in South Africa (CAPRISA). University of KwaZulu-Natal Nelson R Mandela School of Medicine. Durban, South Africa / SA-Medical Research Council (MRC)-CAPRISA-HIV-TB Pathogenesis and Treatment Research Unit. University of KwaZulu-Natal Nelson R Mandela School of Medicine. Durban, South Africa.
School of Clinical Medicine. University of Witwatersrand. Johannesburg. South Africa
HIV Medicine. Joint Clinical Research Centre. Kampala, Uganda.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative. Salvador, BA, Brasil / Universidade Federal da Bahia. Programa de Pós-Graduação em Patologia Humana e Experimental. Salvador, BA, Brasil / Faculdade de Tecnologia e Ciências. Curso de Medicina. Salvador, BA, Brasil.
Department of Medicine. Johns Hopkins University School of Medicine. Baltimore, MD, USA.
Abstract
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.
Keywords in Portuguese
TuberculoseHemoglobina
Inflamação sistêmica
HIV
Incidente TB
Anemia
Inflamação
Morte
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