Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/29551
Title: C-reactive protein (CRP), interferon gamma-inducible protein 10 (IP-10), and lipopolysaccharide (LPS) are associated with risk of tuberculosis after initiation of antiretroviral therapy in resource-limited settings
Authors: Tenforde, Mark W.
Gupte, Nikhil
Dowdy, David W.
Asmuth, David M.
Balagopal, Ashwin
Pollard, Richard B.
Sugandhavesa, Patcharaphan
Lama, Javier R.
Pillay, Sandy
Cardoso, Sandra W.
Pawar, Jyoti
Santos, Breno
Riviere, Cynthia
Mwelase, Noluthando
Kanyama, Cecilia
Kumwenda, Johnstone
Hakim, James G.
Kumarasamy, Nagalingeswaran
Bollinger, Robert
Semba, Richard D.
Campbell, Thomas B.
Gupta, Amita
ACTG PEARLS
NWCS 319 Study Group
Affilliation: Johns Hopkins University School of Medicine. Baltimore, Maryland, United States of America.
Johns Hopkins University School of Medicine. Baltimore, Maryland, United States of America.
Johns Hopkins University Bloomberg School of Public Health. Baltimore, Maryland, United States of America.
University of California Davis Medical Center. Sacramento, California, United States of America.
Johns Hopkins University School of Medicine. Baltimore, Maryland, United States of America.
University of California Davis Medical Center. Sacramento, California, United States of America.
Chiang Mai University. Research Institute for Health Sciences. Chiang Mai, Thailand.
Asociación Civil Impacta Salud y Educación (IMPACTA) Peru Clinical Trials Unit. Lima, Peru.
University of KwaZulu-Natal. Nelson Mandela School of Medicine. Durban, South Africa.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em DST/AIDS. Rio de Janeiro, RJ, Brasil.
National AIDS Research Institute. Pune, India.
Hospital Nossa Senhora da Conceição. Porto Alegre, RS, Brasil.
Les Centres Groupe Haïtien d'Etude du Sarcome de Kaposi et des Infections Opportunites (GHESKIO). Port-Au-Prince, Haiti.
University of Witwatersrand. Johannesburg, South Africa.
University of North Carolina Project. Kamuzu Central Hospital. Lilongwe, Malawi.
Malawi College of Medicine-Johns Hopkins University Research Project. Blantyre, Malawi.
University of Zimbabwe. Harare, Zimbabwe.
Y.R. Gaitonde Centre for AIDS Research and Education (YRG CARE). Chennai, India.
Johns Hopkins University School of Medicine. Baltimore, Maryland, United States of America.
Johns Hopkins University School of Medicine. Baltimore, Maryland, United States of America.
University of Colorado Denver School of Medicine. Aurora, Colorado, United States of America.
Johns Hopkins University School of Medicine. Baltimore, Maryland, United States of America./ Johns Hopkins University Bloomberg School of Public Health. Baltimore, Maryland, United States of America.
Abstract: Objective: The association between pre-antiretroviral (ART) inflammation and immune activation and risk for incident tuberculosis (TB) after ART initiation among adults is uncertain. Design: Nested case-control study (n = 332) within ACTG PEARLS trial of three ART regimens among 1571 HIV-infected, treatment-naïve adults in 9 countries. We compared cases (participants with incident TB diagnosed by 96 weeks) to a random sample of controls (participants who did not develop TB, stratified by country and treatment arm). Methods We measured pre-ART C-reactive protein (CRP), EndoCab IgM, ferritin, interferon gamma (IFN-γ), interleukin 6 (IL-6), interferon gamma-inducible protein 10 (IP-10), lipopolysaccharide (LPS), soluble CD14 (sCD14), tumor necrosis factor alpha (TNF-α), and CD4/DR+/38+ and CD8/DR+/38+ T cells. Markers were defined according to established cutoff definitions when available, 75th percentile of measured values when not, and detectable versus undetectable for LPS. Using logistic regression, we measured associations between biomarkers and incident TB, adjusting for age, sex, study site, treatment arm, baseline CD4 and log10 viral load. We assessed the discriminatory value of biomarkers using receiver operating characteristic (ROC) analysis. Results: Seventy-seven persons (4.9%) developed incident TB during follow-up. Elevated baseline CRP (aOR 3.25, 95% CI: 1.55–6.81) and IP-10 (aOR 1.89, 95% CI: 1.05–3.39), detectable plasma LPS (aOR 2.39, 95% CI: 1.13–5.06), and the established TB risk factors anemia and hypoalbuminemia were independently associated with incident TB. In ROC analysis, CRP, albumin, and LPS improved discrimination only modestly for TB risk when added to baseline routine patient characteristics including CD4 count, body mass index, and prior TB. Conclusion: Incident TB occurs commonly after ART initiation. Although associated with higher postART TB risk, baseline CRP, IP-10, and LPS add limited value to routine patient characteristics in discriminating who develops active TB. Besides determining ideal cutoffs for these biomarkers, additional biomarkers should be sought that predict TB disease in ART initiators.
Keywords: C-Reactive Protein (CRP)
Tuberculosis
Interferon GammaInducible Protein 10 (IP-10)
Lipopolysaccharide (LPS)
Antiretroviral Therapy
Issue Date: 2015
Citation: TENFORDE, Mark W. et al. C-Reactive Protein (CRP), Interferon Gamma-Inducible Protein 10 (IP-10), and Lipopolysaccharide (LPS) Are Associated with Risk of Tuberculosis after Initiation of Antiretroviral Therapy in Resource-Limited Settings. PLoS ONE, v. 10, n. 2, p. 1-16, 2015.
DOI: 10.1371/journal.pone.0117424
ISSN: 1932-6203
Copyright: open access
Appears in Collections:INI - Artigos de Periódicos



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