| Author | Manabe, Yukari C. | |
| Author | Andrade, Bruno de Bezerril | |
| Author | Gupte, Nikhil | |
| Author | Leong, Samantha | |
| Author | Kintali, Manisha | |
| Author | Matoga, Mitch | |
| Author | Riviere, Cynthia | |
| Author | Sameneka, Wadzanai | |
| Author | Lama, Javier R. | |
| Author | Naidoo, Kogieleum | |
| Author | Zhao, Yue | |
| Author | Johnson, W. Evan | |
| Author | Ellner, Jerrold J. | |
| Author | Hosseinipour, Mina C. | |
| Author | Bisson, Gregory P. | |
| Author | Salgame, Padmini | |
| Author | Gupta, Amita | |
| Author | ACTG A5274 REMEMBER and NWCS 408 Study Team | |
| Access date | 2019-12-17T14:15:41Z | |
| Available date | 2019-12-17T14:15:41Z | |
| Document date | 2019 | |
| Citation | MANABE, Yukari C. et al. A Parsimonious Host Inflammatory Biomarker Signature Predicts Incident TB and Mortality in Advanced HIV. Clinical Infectious Diseases, p. 1-25, Nov. 2019. | |
| ISSN | 1058-4838 | |
| URI | https://www.arca.fiocruz.br/handle/icict/38651 | |
| Sponsorship | AIDS Clinical Trials Group which is supported by the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH) under Award Number UM1 AI068634, UM1 AI068636 and UM1 AI106701. The work was also supported by The Johns Hopkins Baltimore-Washington-India Clinical Trials Unit (BWI CTU) (NIH/NIAID UM1AI069465 to AG, NG, and YCM). Additional salary support provided for YCM from the Fogarty International Center at the NIH (D43TW009771). The work of BBA was supported by the intramural research program from FIOCRUZ and from the National Institutes of Health (U01AI115940). | |
| Language | eng | en_US |
| Publisher | Oxford University Press | |
| Rights | open access | |
| Subject in Portuguese | Tuberculose | pt_BR |
| Subject in Portuguese | Biomarcador | pt_BR |
| Subject in Portuguese | Terapia antirretroviral | pt_BR |
| Subject in Portuguese | Mortalidade precoce | pt_BR |
| Title | A Parsimonious Host Inflammatory Biomarker Signature Predicts Incident TB and Mortality in Advanced HIV | en_US |
| Type | Preprint | |
| DOI | 10.1093/cid/ciz1147 | |
| Abstract | People with advanced HIV (CD4<50) remain at high risk of TB or death despite the initiation of antiretroviral therapy. We aimed to identify immunological profiles that were most predictive of incident TB disease and death. METHODS: The REMEMBER randomized clinical trial enrolled 850 participants with HIV (CD4<50 cells/μL) at ART initiation to receive either empiric TB treatment or isoniazid preventive therapy (IPT). A case-cohort study (n=257) stratified by country and treatment arm was performed. Cases were defined as incident TB or all-cause death within 48 weeks after ART initiation. Using multiplexed immunoassay panels and ELISA, 26 biomarkers were assessed in plasma. RESULTS: 52 (6.1%) of 850 participants developed TB; 47 (5.5%) died (13 of whom had antecedent TB). Biomarkers associated with incident TB overlapped with those associated with death (IL-1β, IL-6). Biomarker levels declined over time in individuals with incident TB while remaining persistently elevated in those who died. Dividing the cohort into development and validation sets, the final model of 6 biomarkers (CXCL10, IL-1β, IL-10, sCD14, TNF-α, and TNF-β) achieved a sensitivity of 0.90 (95% CI: 0.87-0.94) and a specificity of 0.71(95% CI: 0.68-0.75) with an area under the curve (AUC) of 0.81 (95% CI: 0.78-0.83) for incident TB. CONCLUSION: Among people with advanced HIV, a parsimonious inflammatory biomarker signature predicted those at highest risk for developing TB despite initiation of ART and TB preventive therapies. The signature may be a promising stratification tool to select patients who may benefit from increased monitoring and novel interventions. | en_US |
| Affilliation | Johns Hopkins University School of Medicine. Department of Medicine. Division of Infectious Diseases. Baltimore, MD, USA. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / José Silveira Foundation. Multinational Organization Network Sponsoring Translational and Epidemiological Research. Salvador, BA, Brazil / University of Cape Town. Institute of Infectious Disease and Molecular Medicine. Wellcome Centre for Infectious Disease Research in Africa. Cape Town, South Africa. | |
| Affilliation | Johns Hopkins University School of Medicine. Department of Medicine. Division of Infectious Diseases. Baltimore, MD, USA / Johns Hopkins University Clinical Research Site. Byramjee-Jeejeebhoy Government Medical College. Pune, India. | |
| Affilliation | Center for Emerging Pathogens, Rutgers. New Jersey Medical School. Department of Medicine. Newark, NJ, USA. | |
| Affilliation | Center for Emerging Pathogens, Rutgers. New Jersey Medical School. Department of Medicine. Newark, NJ, USA. | |
| Affilliation | UNC Project Malawi. Lilongwe Malawi. | |
| Affilliation | Les Centres GHESKIO Clinical Research Site. Port au prince, Haiti. | |
| Affilliation | University of Zimbabwe. College of Health Sciences-Clinical. Trials Research Centre. Harare, Zimbabwe. | |
| Affilliation | Asociacion Civil Impacta Salud y Educacion. Lima, Peru. | |
| Affilliation | University of KwaZulu-Natal. Centre for the AIDS Programme of Research in South Africa. Durban, South Africa / University of Kwa Zulu-Natal. Doris Duke Medical Research Institute. Pathogenesis and Treatment Research. Durban, South Africa. | |
| Affilliation | Boston Medical Center. Department of Medicine. Boston, MA, USA. | |
| Affilliation | Boston Medical Center. Department of Medicine. Boston, MA, USA. | |
| Affilliation | Center for Emerging Pathogens, Rutgers. New Jersey Medical School. Department of Medicine. Newark, NJ, USA. | |
| Affilliation | Les Centres GHESKIO Clinical Research Site. Port au prince, Haiti / University of North Carolina School of Medicine. Division of Infectious Diseases. Department of Medicine. Chapel Hill, NC, USA. | |
| Affilliation | University of Pennsylvania. Perelman School of Medicine. Division of Infectious Diseases. Department of Medicine. Philadelphia, PA, USA. | |
| Affilliation | Center for Emerging Pathogens, Rutgers. New Jersey Medical School. Department of Medicine. Newark, NJ, USA. | |
| Affilliation | Johns Hopkins University School of Medicine. Department of Medicine. Division of Infectious Diseases. Baltimore, MD, USA. | |
| Subject | Tuberculosis | en_US |
| Subject | Biomarker | en_US |
| Subject | Antiretroviral therapy | en_US |
| Subject | Early mortality | en_US |
| xmlui.metadata.dc.subject.ods | 03 Saúde e Bem-Estar | |
