Inflammatory profile of patients with tuberculosis with or without HIV-1 co-infection: a prospective cohort study and immunological network analysis.

Autor:	Bruyn ED; Wellcome Centre for Infectious Disease Research in Africa, Institute of Infectious Disease and Molecular Medicine (E Du Bruyn MD, N Rockwood PhD, C Schutz MD, G Meintjes PhD, C Riou PhD, K A Wilkinson PhD, B B Andrade MD, Prof R J Wilkinson FMedSci) and Department of Medicine (E Du Bruyn, C Schutz, G Meintjes, Prof R J Wilkinson), University of Cape Town, Observatory, South Africa; Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Brazil (K F Fukutani PhD, M B Arriaga MSc, J M Cubillos-Angulo MSc, R Tibúrcio MSc, B B Andrade); Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative, Salvador, Brazil (K F Fukutani, M B Arriaga, J M Cubillos-Angulo, R Tibúrcio, B B Andrade); Curso de Medicina, Faculdade de Tecnologia e Ciências, Salvador, Brazil (K F Fukutani); Department of Infectious Diseases, Imperial College London, London, UK (N Rockwood, Prof R J Wilkinson); Department of Microbiology, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka (N Rockwood); Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA (A Sher PhD); The Francis Crick Institute, London, UK (K A Wilkinson, Prof R J Wilkinson); Universidade Salvador, Laureate Universities, Salvador, Brazil (B B Andrade); Escola Bahiana de Medicina e Saúde Pública, Salvador, Brazil (B B Andrade); Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA (B B Andrade)., Fukutani KF; Wellcome Centre for Infectious Disease Research in Africa, Institute of Infectious Disease and Molecular Medicine (E Du Bruyn MD, N Rockwood PhD, C Schutz MD, G Meintjes PhD, C Riou PhD, K A Wilkinson PhD, B B Andrade MD, Prof R J Wilkinson FMedSci) and Department of Medicine (E Du Bruyn, C Schutz, G Meintjes, Prof R J Wilkinson), University of Cape Town, Observatory, South Africa; Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Brazil (K F Fukutani PhD, M B Arriaga MSc, J M Cubillos-Angulo MSc, R Tibúrcio MSc, B B Andrade); Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative, Salvador, Brazil (K F Fukutani, M B Arriaga, J M Cubillos-Angulo, R Tibúrcio, B B Andrade); Curso de Medicina, Faculdade de Tecnologia e Ciências, Salvador, Brazil (K F Fukutani); Department of Infectious Diseases, Imperial College London, London, UK (N Rockwood, Prof R J Wilkinson); Department of Microbiology, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka (N Rockwood); Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA (A Sher PhD); The Francis Crick Institute, London, UK (K A Wilkinson, Prof R J Wilkinson); Universidade Salvador, Laureate Universities, Salvador, Brazil (B B Andrade); Escola Bahiana de Medicina e Saúde Pública, Salvador, Brazil (B B Andrade); Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA (B B Andrade)., Rockwood N; Wellcome Centre for Infectious Disease Research in Africa, Institute of Infectious Disease and Molecular Medicine (E Du Bruyn MD, N Rockwood PhD, C Schutz MD, G Meintjes PhD, C Riou PhD, K A Wilkinson PhD, B B Andrade MD, Prof R J Wilkinson FMedSci) and Department of Medicine (E Du Bruyn, C Schutz, G Meintjes, Prof R J Wilkinson), University of Cape Town, Observatory, South Africa; Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Brazil (K F Fukutani PhD, M B Arriaga MSc, J M Cubillos-Angulo MSc, R Tibúrcio MSc, B B Andrade); Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative, Salvador, Brazil (K F Fukutani, M B Arriaga, J M Cubillos-Angulo, R Tibúrcio, B B Andrade); Curso de Medicina, Faculdade de Tecnologia e Ciências, Salvador, Brazil (K F Fukutani); Department of Infectious Diseases, Imperial College London, London, UK (N Rockwood, Prof R J Wilkinson); Department of Microbiology, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka (N Rockwood); Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA (A Sher PhD); The Francis Crick Institute, London, UK (K A Wilkinson, Prof R J Wilkinson); Universidade Salvador, Laureate Universities, Salvador, Brazil (B B Andrade); Escola Bahiana de Medicina e Saúde Pública, Salvador, Brazil (B B Andrade); Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA (B B Andrade)., Schutz C; Wellcome Centre for Infectious Disease Research in Africa, Institute of Infectious Disease and Molecular Medicine (E Du Bruyn MD, N Rockwood PhD, C Schutz MD, G Meintjes PhD, C Riou PhD, K A Wilkinson PhD, B B Andrade MD, Prof R J Wilkinson FMedSci) and Department of Medicine (E Du Bruyn, C Schutz, G Meintjes, Prof R J Wilkinson), University of Cape Town, Observatory, South Africa; Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Brazil (K F Fukutani PhD, M B Arriaga MSc, J M Cubillos-Angulo MSc, R Tibúrcio MSc, B B Andrade); Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative, Salvador, Brazil (K F Fukutani, M B Arriaga, J M Cubillos-Angulo, R Tibúrcio, B B Andrade); Curso de Medicina, Faculdade de Tecnologia e Ciências, Salvador, Brazil (K F Fukutani); Department of Infectious Diseases, Imperial College London, London, UK (N Rockwood, Prof R J Wilkinson); Department of Microbiology, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka (N Rockwood); Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA (A Sher PhD); The Francis Crick Institute, London, UK (K A Wilkinson, Prof R J Wilkinson); Universidade Salvador, Laureate Universities, Salvador, Brazil (B B Andrade); Escola Bahiana de Medicina e Saúde Pública, Salvador, Brazil (B B Andrade); Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA (B B Andrade)., Meintjes G; Wellcome Centre for Infectious Disease Research in Africa, Institute of Infectious Disease and Molecular Medicine (E Du Bruyn MD, N Rockwood PhD, C Schutz MD, G Meintjes PhD, C Riou PhD, K A Wilkinson PhD, B B Andrade MD, Prof R J Wilkinson FMedSci) and Department of Medicine (E Du Bruyn, C Schutz, G Meintjes, Prof R J Wilkinson), University of Cape Town, Observatory, South Africa; Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Brazil (K F Fukutani PhD, M B Arriaga MSc, J M Cubillos-Angulo MSc, R Tibúrcio MSc, B B Andrade); Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative, Salvador, Brazil (K F Fukutani, M B Arriaga, J M Cubillos-Angulo, R Tibúrcio, B B Andrade); Curso de Medicina, Faculdade de Tecnologia e Ciências, Salvador, Brazil (K F Fukutani); Department of Infectious Diseases, Imperial College London, London, UK (N Rockwood, Prof R J Wilkinson); Department of Microbiology, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka (N Rockwood); Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA (A Sher PhD); The Francis Crick Institute, London, UK (K A Wilkinson, Prof R J Wilkinson); Universidade Salvador, Laureate Universities, Salvador, Brazil (B B Andrade); Escola Bahiana de Medicina e Saúde Pública, Salvador, Brazil (B B Andrade); Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA (B B Andrade)., Arriaga MB; Wellcome Centre for Infectious Disease Research in Africa, Institute of Infectious Disease and Molecular Medicine (E Du Bruyn MD, N Rockwood PhD, C Schutz MD, G Meintjes PhD, C Riou PhD, K A Wilkinson PhD, B B Andrade MD, Prof R J Wilkinson FMedSci) and Department of Medicine (E Du Bruyn, C Schutz, G Meintjes, Prof R J Wilkinson), University of Cape Town, Observatory, South Africa; Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Brazil (K F Fukutani PhD, M B Arriaga MSc, J M Cubillos-Angulo MSc, R Tibúrcio MSc, B B Andrade); Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative, Salvador, Brazil (K F Fukutani, M B Arriaga, J M Cubillos-Angulo, R Tibúrcio, B B Andrade); Curso de Medicina, Faculdade de Tecnologia e Ciências, Salvador, Brazil (K F Fukutani); Department of Infectious Diseases, Imperial College London, London, UK (N Rockwood, Prof R J Wilkinson); Department of Microbiology, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka (N Rockwood); Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA (A Sher PhD); The Francis Crick Institute, London, UK (K A Wilkinson, Prof R J Wilkinson); Universidade Salvador, Laureate Universities, Salvador, Brazil (B B Andrade); Escola Bahiana de Medicina e Saúde Pública, Salvador, Brazil (B B Andrade); Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA (B B Andrade)., Cubillos-Angulo JM; Wellcome Centre for Infectious Disease Research in Africa, Institute of Infectious Disease and Molecular Medicine (E Du Bruyn MD, N Rockwood PhD, C Schutz MD, G Meintjes PhD, C Riou PhD, K A Wilkinson PhD, B B Andrade MD, Prof R J Wilkinson FMedSci) and Department of Medicine (E Du Bruyn, C Schutz, G Meintjes, Prof R J Wilkinson), University of Cape Town, Observatory, South Africa; Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Brazil (K F Fukutani PhD, M B Arriaga MSc, J M Cubillos-Angulo MSc, R Tibúrcio MSc, B B Andrade); Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative, Salvador, Brazil (K F Fukutani, M B Arriaga, J M Cubillos-Angulo, R Tibúrcio, B B Andrade); Curso de Medicina, Faculdade de Tecnologia e Ciências, Salvador, Brazil (K F Fukutani); Department of Infectious Diseases, Imperial College London, London, UK (N Rockwood, Prof R J Wilkinson); Department of Microbiology, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka (N Rockwood); Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA (A Sher PhD); The Francis Crick Institute, London, UK (K A Wilkinson, Prof R J Wilkinson); Universidade Salvador, Laureate Universities, Salvador, Brazil (B B Andrade); Escola Bahiana de Medicina e Saúde Pública, Salvador, Brazil (B B Andrade); Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA (B B Andrade)., Tibúrcio R; Wellcome Centre for Infectious Disease Research in Africa, Institute of Infectious Disease and Molecular Medicine (E Du Bruyn MD, N Rockwood PhD, C Schutz MD, G Meintjes PhD, C Riou PhD, K A Wilkinson PhD, B B Andrade MD, Prof R J Wilkinson FMedSci) and Department of Medicine (E Du Bruyn, C Schutz, G Meintjes, Prof R J Wilkinson), University of Cape Town, Observatory, South Africa; Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Brazil (K F Fukutani PhD, M B Arriaga MSc, J M Cubillos-Angulo MSc, R Tibúrcio MSc, B B Andrade); Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative, Salvador, Brazil (K F Fukutani, M B Arriaga, J M Cubillos-Angulo, R Tibúrcio, B B Andrade); Curso de Medicina, Faculdade de Tecnologia e Ciências, Salvador, Brazil (K F Fukutani); Department of Infectious Diseases, Imperial College London, London, UK (N Rockwood, Prof R J Wilkinson); Department of Microbiology, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka (N Rockwood); Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA (A Sher PhD); The Francis Crick Institute, London, UK (K A Wilkinson, Prof R J Wilkinson); Universidade Salvador, Laureate Universities, Salvador, Brazil (B B Andrade); Escola Bahiana de Medicina e Saúde Pública, Salvador, Brazil (B B Andrade); Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA (B B Andrade)., Sher A; Wellcome Centre for Infectious Disease Research in Africa, Institute of Infectious Disease and Molecular Medicine (E Du Bruyn MD, N Rockwood PhD, C Schutz MD, G Meintjes PhD, C Riou PhD, K A Wilkinson PhD, B B Andrade MD, Prof R J Wilkinson FMedSci) and Department of Medicine (E Du Bruyn, C Schutz, G Meintjes, Prof R J Wilkinson), University of Cape Town, Observatory, South Africa; Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Brazil (K F Fukutani PhD, M B Arriaga MSc, J M Cubillos-Angulo MSc, R Tibúrcio MSc, B B Andrade); Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative, Salvador, Brazil (K F Fukutani, M B Arriaga, J M Cubillos-Angulo, R Tibúrcio, B B Andrade); Curso de Medicina, Faculdade de Tecnologia e Ciências, Salvador, Brazil (K F Fukutani); Department of Infectious Diseases, Imperial College London, London, UK (N Rockwood, Prof R J Wilkinson); Department of Microbiology, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka (N Rockwood); Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA (A Sher PhD); The Francis Crick Institute, London, UK (K A Wilkinson, Prof R J Wilkinson); Universidade Salvador, Laureate Universities, Salvador, Brazil (B B Andrade); Escola Bahiana de Medicina e Saúde Pública, Salvador, Brazil (B B Andrade); Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA (B B Andrade)., Riou C; Wellcome Centre for Infectious Disease Research in Africa, Institute of Infectious Disease and Molecular Medicine (E Du Bruyn MD, N Rockwood PhD, C Schutz MD, G Meintjes PhD, C Riou PhD, K A Wilkinson PhD, B B Andrade MD, Prof R J Wilkinson FMedSci) and Department of Medicine (E Du Bruyn, C Schutz, G Meintjes, Prof R J Wilkinson), University of Cape Town, Observatory, South Africa; Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Brazil (K F Fukutani PhD, M B Arriaga MSc, J M Cubillos-Angulo MSc, R Tibúrcio MSc, B B Andrade); Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative, Salvador, Brazil (K F Fukutani, M B Arriaga, J M Cubillos-Angulo, R Tibúrcio, B B Andrade); Curso de Medicina, Faculdade de Tecnologia e Ciências, Salvador, Brazil (K F Fukutani); Department of Infectious Diseases, Imperial College London, London, UK (N Rockwood, Prof R J Wilkinson); Department of Microbiology, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka (N Rockwood); Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA (A Sher PhD); The Francis Crick Institute, London, UK (K A Wilkinson, Prof R J Wilkinson); Universidade Salvador, Laureate Universities, Salvador, Brazil (B B Andrade); Escola Bahiana de Medicina e Saúde Pública, Salvador, Brazil (B B Andrade); Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA (B B Andrade)., Wilkinson KA; Wellcome Centre for Infectious Disease Research in Africa, Institute of Infectious Disease and Molecular Medicine (E Du Bruyn MD, N Rockwood PhD, C Schutz MD, G Meintjes PhD, C Riou PhD, K A Wilkinson PhD, B B Andrade MD, Prof R J Wilkinson FMedSci) and Department of Medicine (E Du Bruyn, C Schutz, G Meintjes, Prof R J Wilkinson), University of Cape Town, Observatory, South Africa; Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Brazil (K F Fukutani PhD, M B Arriaga MSc, J M Cubillos-Angulo MSc, R Tibúrcio MSc, B B Andrade); Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative, Salvador, Brazil (K F Fukutani, M B Arriaga, J M Cubillos-Angulo, R Tibúrcio, B B Andrade); Curso de Medicina, Faculdade de Tecnologia e Ciências, Salvador, Brazil (K F Fukutani); Department of Infectious Diseases, Imperial College London, London, UK (N Rockwood, Prof R J Wilkinson); Department of Microbiology, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka (N Rockwood); Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA (A Sher PhD); The Francis Crick Institute, London, UK (K A Wilkinson, Prof R J Wilkinson); Universidade Salvador, Laureate Universities, Salvador, Brazil (B B Andrade); Escola Bahiana de Medicina e Saúde Pública, Salvador, Brazil (B B Andrade); Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA (B B Andrade)., Andrade BB; Wellcome Centre for Infectious Disease Research in Africa, Institute of Infectious Disease and Molecular Medicine (E Du Bruyn MD, N Rockwood PhD, C Schutz MD, G Meintjes PhD, C Riou PhD, K A Wilkinson PhD, B B Andrade MD, Prof R J Wilkinson FMedSci) and Department of Medicine (E Du Bruyn, C Schutz, G Meintjes, Prof R J Wilkinson), University of Cape Town, Observatory, South Africa; Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Brazil (K F Fukutani PhD, M B Arriaga MSc, J M Cubillos-Angulo MSc, R Tibúrcio MSc, B B Andrade); Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative, Salvador, Brazil (K F Fukutani, M B Arriaga, J M Cubillos-Angulo, R Tibúrcio, B B Andrade); Curso de Medicina, Faculdade de Tecnologia e Ciências, Salvador, Brazil (K F Fukutani); Department of Infectious Diseases, Imperial College London, London, UK (N Rockwood, Prof R J Wilkinson); Department of Microbiology, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka (N Rockwood); Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA (A Sher PhD); The Francis Crick Institute, London, UK (K A Wilkinson, Prof R J Wilkinson); Universidade Salvador, Laureate Universities, Salvador, Brazil (B B Andrade); Escola Bahiana de Medicina e Saúde Pública, Salvador, Brazil (B B Andrade); Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA (B B Andrade)., Wilkinson RJ; Wellcome Centre for Infectious Disease Research in Africa, Institute of Infectious Disease and Molecular Medicine (E Du Bruyn MD, N Rockwood PhD, C Schutz MD, G Meintjes PhD, C Riou PhD, K A Wilkinson PhD, B B Andrade MD, Prof R J Wilkinson FMedSci) and Department of Medicine (E Du Bruyn, C Schutz, G Meintjes, Prof R J Wilkinson), University of Cape Town, Observatory, South Africa; Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Brazil (K F Fukutani PhD, M B Arriaga MSc, J M Cubillos-Angulo MSc, R Tibúrcio MSc, B B Andrade); Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative, Salvador, Brazil (K F Fukutani, M B Arriaga, J M Cubillos-Angulo, R Tibúrcio, B B Andrade); Curso de Medicina, Faculdade de Tecnologia e Ciências, Salvador, Brazil (K F Fukutani); Department of Infectious Diseases, Imperial College London, London, UK (N Rockwood, Prof R J Wilkinson); Department of Microbiology, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka (N Rockwood); Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA (A Sher PhD); The Francis Crick Institute, London, UK (K A Wilkinson, Prof R J Wilkinson); Universidade Salvador, Laureate Universities, Salvador, Brazil (B B Andrade); Escola Bahiana de Medicina e Saúde Pública, Salvador, Brazil (B B Andrade); Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA (B B Andrade).
Jazyk:	angličtina
Zdroj:	The Lancet. Microbe [Lancet Microbe] 2021 Aug; Vol. 2 (8), pp. e375-e385. Date of Electronic Publication: 2021 May 18.
DOI:	10.1016/s2666-5247(21)00037-9
Abstrakt:	Background: HIV-1 mediated dysregulation of the immune response to tuberculosis and its effect on the response to antitubercular therapy (ATT) is incompletely understood. We aimed to analyse the inflammatory profile of patients with tuberculosis with or without HIV-1 co-infection undergoing ATT, with specific focus on the effect of ART and HIV-1 viraemia in those co-infected with HIV-1. Methods: In this prospective cohort study and immunological network analysis, a panel of 38 inflammatory markers were measured in the plasma of a prospective patient cohort undergoing ATT at Khayelitsha Site B clinic, Cape Town, South Africa. We recruited patients with sputum Xpert MTB/RIF-positive rifampicin-susceptible pulmonary tuberculosis. Patients were excluded from the primary discovery cohort if they were younger than 18 years, unable to commence ATT for any reason, pregnant, had unknown HIV-1 status, were unable to consent to study participation, were unable to provide baseline sputum samples, had more than three doses of ATT, or were being re-treated for tuberculosis within 6 months of their previous ATT regimen. Plasma samples were collected at baseline (1-5 days after commencing ATT), week 8, and week 20 of ATT. We applied network and multivariate analysis to investigate the dynamic inflammatory profile of these patients in relation to ATT and by HIV status. In addition to the discovery cohort, a validation cohort of patients with HIV-1 admitted to hospital with CD4 counts less than 350 cells per μL and a high clinical suspicion of new tuberculosis were recruited. Findings: Between March 1, 2013, and July 31, 2014, we assessed a cohort of 129 participants (55 [43%] female and 74 [57%] male, median age 35·1 years [IQR 30·1-43·7]) and 76 were co-infected with HIV-1. HIV-1 status markedly influenced the inflammatory profile regardless of ATT duration. HIV-1 viral load emerged as a major factor driving differential inflammatory marker expression and having a strong effect on correlation profiles observed in the HIV-1 co-infected group. Interleukin (IL)-17A emerged as a key correlate of HIV-1-induced inflammation during HIV-tuberculosis co-infection. Interpretation: Our findings show the effect of HIV-1 co-infection on the complexity of plasma inflammatory profiles in patients with tuberculosis. Through network analysis we identified IL-17A as an important node in HIV-tuberculosis co-infection, thus implicating this cytokine's capacity to correlate with, and regulate, other inflammatory markers. Further mechanistic studies are required to identify specific IL-17A-related inflammatory pathways mediating immunopathology in HIV-tuberculosis co-infection, which could illuminate targets for future host-directed therapies. Funding: National Institutes of Health, The Wellcome Trust, UK Research and Innovation, Cancer Research UK, European and Developing Countries Clinical Trials Partnership, and South African Medical Research Council.
Databáze:	MEDLINE
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