PMID- 24795473 OWN - NLM STAT- MEDLINE DCOM- 20141117 LR - 20220408 IS - 1537-6613 (Electronic) IS - 0022-1899 (Print) IS - 0022-1899 (Linking) VI - 210 IP - 8 DP - 2014 Oct 15 TI - Soluble markers of inflammation and coagulation but not T-cell activation predict non-AIDS-defining morbid events during suppressive antiretroviral treatment. PG - 1248-59 LID - 10.1093/infdis/jiu254 [doi] AB - 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. CI - (c) The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com. FAU - Tenorio, Allan R AU - Tenorio AR AD - Department of Medicine. FAU - Zheng, Yu AU - Zheng Y AD - Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, Massachusetts. FAU - Bosch, Ronald J AU - Bosch RJ AD - Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, Massachusetts. FAU - Krishnan, Supriya AU - Krishnan S AD - Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, Massachusetts. FAU - Rodriguez, Benigno AU - Rodriguez B AD - Division of Infectious Diseases and HIV Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio. FAU - Hunt, Peter W AU - Hunt PW AD - Positive Health Program, Department of Medicine, San Francisco General Hospital, University of California; FAU - Plants, Jill AU - Plants J AD - Department of Immunology and Microbiology, Rush University Medical Center, Chicago, Illinois. FAU - Seth, Arjun AU - Seth A AD - Division of Infectious Diseases and HIV Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio. FAU - Wilson, Cara C AU - Wilson CC AD - Division of Infectious Diseases, University of Colorado Hospital, Aurora. FAU - Deeks, Steven G AU - Deeks SG AD - Positive Health Program, Department of Medicine, San Francisco General Hospital, University of California; FAU - Lederman, Michael M AU - Lederman MM AD - Division of Infectious Diseases and HIV Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio. FAU - Landay, Alan L AU - Landay AL AD - Department of Immunology and Microbiology, Rush University Medical Center, Chicago, Illinois. LA - eng SI - ClinicalTrials.gov/NCT00001137 GR - P30 MH062246/MH/NIMH NIH HHS/United States GR - AI36219/AI/NIAID NIH HHS/United States GR - K24 AI069994/AI/NIAID NIH HHS/United States GR - UM1 AI068634/AI/NIAID NIH HHS/United States GR - R21 AI087035/AI/NIAID NIH HHS/United States GR - AI068636/AI/NIAID NIH HHS/United States GR - U01 AI068636/AI/NIAID NIH HHS/United States GR - UM1 AI069496/AI/NIAID NIH HHS/United States GR - P30 AI027763/AI/NIAID NIH HHS/United States GR - UM1 AI106701/AI/NIAID NIH HHS/United States GR - P30 AI036219/AI/NIAID NIH HHS/United States GR - U01 AI069471/AI/NIAID NIH HHS/United States GR - U01 AI068634/AI/NIAID NIH HHS/United States GR - UM1 AI068636/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20140501 PL - United States TA - J Infect Dis JT - The Journal of infectious diseases JID - 0413675 RN - 0 (Anti-HIV Agents) RN - 0 (Biomarkers) RN - 0 (RNA, Viral) SB - IM CIN - J Infect Dis. 2015 May 1;211(9):1511-3. PMID: 25398457 CIN - J Infect Dis. 2015 May 1;211(9):1514-5. PMID: 25398458 MH - Adult MH - Aged MH - Anti-HIV Agents/*therapeutic use MH - Biomarkers/metabolism MH - Blood Coagulation/*physiology MH - Case-Control Studies MH - Female MH - HIV Infections/complications/*drug therapy MH - Humans MH - Inflammation/*metabolism MH - Lymphocyte Activation/*drug effects MH - Male MH - Middle Aged MH - RNA, Viral/blood MH - T-Lymphocytes/*physiology MH - Viral Load MH - Young Adult PMC - PMC4192039 OTO - NOTNLM OT - ART OT - HIV OT - Non-AIDS morbidity OT - immune activation OT - inflammation EDAT- 2014/05/06 06:00 MHDA- 2014/11/18 06:00 PMCR- 2015/10/15 CRDT- 2014/05/06 06:00 PHST- 2014/05/06 06:00 [entrez] PHST- 2014/05/06 06:00 [pubmed] PHST- 2014/11/18 06:00 [medline] PHST- 2015/10/15 00:00 [pmc-release] AID - jiu254 [pii] AID - 10.1093/infdis/jiu254 [doi] PST - ppublish SO - J Infect Dis. 2014 Oct 15;210(8):1248-59. doi: 10.1093/infdis/jiu254. Epub 2014 May 1.