Allan R Tenorio1, Yu Zheng2, Ronald J Bosch2, Supriya Krishnan2, Benigno Rodriguez3, Peter W Hunt4, Jill Plants5, Arjun Seth3, Cara C Wilson6, Steven G Deeks4, Michael M Lederman3, Alan L Landay5. 1. Department of Medicine. 2. Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, Massachusetts. 3. Division of Infectious Diseases and HIV Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio. 4. Positive Health Program, Department of Medicine, San Francisco General Hospital, University of California; 5. Department of Immunology and Microbiology, Rush University Medical Center, Chicago, Illinois. 6. Division of Infectious Diseases, University of Colorado Hospital, Aurora.
Abstract
BACKGROUND: Defining the association of non-AIDS-defining events with inflammation and immune activation among human immunodeficiency virus (HIV)-infected persons with antiretroviral therapy (ART)-associated virological suppression is critical to identifying interventions to decrease the occurrence of these events. METHODS: We conducted a case-control study of HIV-infected subjects who had achieved virological suppression within 1 year after ART initiation. Cases were patients who experienced non-AIDS-defining events, defined as myocardial infarction, stroke, non-AIDS-defining cancer, non-AIDS-defining serious bacterial infection, or death. Controls were matched to cases on the basis of age, sex, pre-ART CD4(+) T-cell count, and ART regimen. Peripheral blood mononuclear cells and plasma specimens obtained at the visit before ART initiation (hereafter, baseline), the visit approximately 1 year after ART initiation (hereafter, year 1), and the visit immediately preceding the non-AIDS-defining event (hereafter, pre-event) were analyzed for activated CD4(+) and CD8(+) T cells, plasma interleukin 6 (IL-6) level, soluble tumor necrosis factor receptor I (sTNFR-I) level, sTNFR-II level, soluble CD14 level, kynurenine-to-tryptophan (KT) ratio, and D-dimer level. Conditional logistic regression analysis was used to study the association between biomarkers and outcomes, with adjustment for potential confounders. RESULTS: Higher IL-6 level, sTNFR-I level, sTNFR-II level, KT ratio, and D-dimer level at year 1 were associated with the occurrence of a non-AIDS-defining event. Significant associations were also seen between non-AIDS-defining events and values of these biomarkers in specimens obtained at baseline and the pre-event time points. Effects remained significant after control for confounders. T-cell activation was not significantly related to outcomes. CONCLUSIONS: Interventional trials to decrease the incidence of non-AIDS-defining events among HIV-infected persons with virological suppression should consider targeting the pathways represented by these soluble markers. Clinical Trials Registration. NCT00001137.
BACKGROUND: Defining the association of non-AIDS-defining events with inflammation and immune activation among human immunodeficiency virus (HIV)-infectedpersons with antiretroviral therapy (ART)-associated virological suppression is critical to identifying interventions to decrease the occurrence of these events. METHODS: We conducted a case-control study of HIV-infected subjects who had achieved virological suppression within 1 year after ART initiation. Cases were patients who experienced non-AIDS-defining events, defined as myocardial infarction, stroke, non-AIDS-defining cancer, non-AIDS-defining serious bacterial infection, or death. Controls were matched to cases on the basis of age, sex, pre-ART CD4(+) T-cell count, and ART regimen. Peripheral blood mononuclear cells and plasma specimens obtained at the visit before ART initiation (hereafter, baseline), the visit approximately 1 year after ART initiation (hereafter, year 1), and the visit immediately preceding the non-AIDS-defining event (hereafter, pre-event) were analyzed for activated CD4(+) and CD8(+) T cells, plasma interleukin 6 (IL-6) level, soluble tumornecrosis factor receptor I (sTNFR-I) level, sTNFR-II level, soluble CD14 level, kynurenine-to-tryptophan (KT) ratio, and D-dimer level. Conditional logistic regression analysis was used to study the association between biomarkers and outcomes, with adjustment for potential confounders. RESULTS: Higher IL-6 level, sTNFR-I level, sTNFR-II level, KT ratio, and D-dimer level at year 1 were associated with the occurrence of a non-AIDS-defining event. Significant associations were also seen between non-AIDS-defining events and values of these biomarkers in specimens obtained at baseline and the pre-event time points. Effects remained significant after control for confounders. T-cell activation was not significantly related to outcomes. CONCLUSIONS: Interventional trials to decrease the incidence of non-AIDS-defining events among HIV-infectedpersons with virological suppression should consider targeting the pathways represented by these soluble markers. Clinical Trials Registration. NCT00001137.
Authors: Kaku A Armah; Kathleen McGinnis; Jason Baker; Cynthia Gibert; Adeel A Butt; Kendall J Bryant; Matthew Goetz; Russell Tracy; Krisann K Oursler; David Rimland; Kristina Crothers; Maria Rodriguez-Barradas; Steve Crystal; Adam Gordon; Kevin Kraemer; Sheldon Brown; Mariana Gerschenson; David A Leaf; Steven G Deeks; Charles Rinaldo; Lewis H Kuller; Amy Justice; Matthew Freiberg Journal: Clin Infect Dis Date: 2012-04-24 Impact factor: 9.079
Authors: Peter W Hunt; Huyen L Cao; Conrad Muzoora; Isaac Ssewanyana; John Bennett; Nneka Emenyonu; Annet Kembabazi; Torsten B Neilands; David R Bangsberg; Steven G Deeks; Jeffrey N Martin Journal: AIDS Date: 2011-11-13 Impact factor: 4.177
Authors: Silvia Giovannini; Graziano Onder; Rosa Liperoti; Andrea Russo; Christy Carter; Ettore Capoluongo; Marco Pahor; Roberto Bernabei; Francesco Landi Journal: J Am Geriatr Soc Date: 2011-08-24 Impact factor: 5.562
Authors: Tricia H Burdo; Janet Lo; Suhny Abbara; Jeffrey Wei; Michelle E DeLelys; Fred Preffer; Eric S Rosenberg; Kenneth C Williams; Steven Grinspoon Journal: J Infect Dis Date: 2011-10-15 Impact factor: 5.226
Authors: Carey L Shive; Angélique Biancotto; Nicholas T Funderburg; Heather A Pilch-Cooper; Hernan Valdez; Leonid Margolis; Scott F Sieg; Grace A McComsey; Benigno Rodriguez; Michael M Lederman Journal: J Acquir Immune Defic Syndr Date: 2012-10-01 Impact factor: 3.731
Authors: David R Boulware; Katherine Huppler Hullsiek; Camille E Puronen; Adam Rupert; Jason V Baker; Martyn A French; Paul R Bohjanen; Richard M Novak; James D Neaton; Irini Sereti Journal: J Infect Dis Date: 2011-06-01 Impact factor: 5.226
Authors: Daniel A Duprez; Jacqueline Neuhaus; Lewis H Kuller; Russell Tracy; Waldo Belloso; Stephane De Wit; Fraser Drummond; H Clifford Lane; Bruno Ledergerber; Jens Lundgren; Daniel Nixon; Nicholas I Paton; Ronald J Prineas; James D Neaton Journal: PLoS One Date: 2012-09-10 Impact factor: 3.240
Authors: Nels C Olson; Margaret F Doyle; Nancy Swords Jenny; Sally A Huber; Bruce M Psaty; Richard A Kronmal; Russell P Tracy Journal: PLoS One Date: 2013-08-23 Impact factor: 3.240
Authors: Michael L Freeman; Joseph C Mudd; Carey L Shive; Souheil-Antoine Younes; Soumya Panigrahi; Scott F Sieg; Sulggi A Lee; Peter W Hunt; Leonard H Calabrese; Sara Gianella; Benigno Rodriguez; Michael M Lederman Journal: Clin Infect Dis Date: 2015-09-23 Impact factor: 9.079
Authors: Theodoros Kelesidis; Carlee Moser; James H Stein; Todd T Brown; Thuy Tien T Tran; Heather J Ribaudo; Michael P Dube; Otto O Yang; Judith S Currier; Grace A McComsey Journal: J Infect Dis Date: 2016-06-28 Impact factor: 5.226
Authors: Theodoros Kelesidis; Thuy Tien T Tran; James H Stein; Todd T Brown; Carlee Moser; Heather J Ribaudo; Michael P Dube; Robert Murphy; Otto O Yang; Judith S Currier; Grace A McComsey Journal: Clin Infect Dis Date: 2015-04-22 Impact factor: 9.079
Authors: Jose R Castillo-Mancilla; Todd T Brown; Kristine M Erlandson; Frank J Palella; Edward M Gardner; Bernard J C Macatangay; Elizabeth C Breen; Lisa P Jacobson; Peter L Anderson; Nikolas I Wada Journal: Clin Infect Dis Date: 2016-09-22 Impact factor: 9.079
Authors: Jessica L Castilho; Bryan E Shepherd; John Koethe; Megan Turner; Sally Bebawy; James Logan; William B Rogers; Stephen Raffanti; Timothy R Sterling Journal: AIDS Date: 2016-03-27 Impact factor: 4.177
Authors: Michael L Freeman; Carey L Shive; Thao P Nguyen; Souheil-Antoine Younes; Soumya Panigrahi; Michael M Lederman Journal: J Infect Dis Date: 2016-10-01 Impact factor: 5.226