Gut epithelial barrier dysfunction and innate immune activation predict mortality in treated HIV infection

Journal of Infectious Diseases

Volumn 210, Issue 8, 2014, Pages 1228-1238

  Hunt, Peter W ^a   Sinclair, Elizabeth ^a   Rodriguez, Benigno ^b   Shive, Carey ^b   Clagett, Brian ^b   Funderburg, Nicholas ^c   Robinson, Janet ^b   Huang, Yong ^d   Epling, Lorrie ^a   Martin, Jeffrey N ^a,e   Deeks, Steven G ^a   Meinert, Curtis L ^f   Van Natta, Mark L ^f   Jabs, Douglas A ^f,g   Lederman, Michael M ^b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b CASE WESTERN RESERVE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c OHIO STATE UNIVERSITY   (United States)

^d Department of Bioengineering and Therapeutic Sciences ^*  (United States)

^e UNIVERSITY OF CALIFORNIA   (United States)

^f JOHNS HOPKINS UNIVERSITY   (United States)

^g MOUNT SINAI SCHOOL OF MEDICINE   (United States)

Author keywords

Antiretroviral therapy; CD28; CD38; CD57; Cytomegalovirus; D dimer; Gut epithelial cell barrier; HIV; HLA DR; hsCRP; IL 6; Immune activation; Intestinal fatty acid binding protein (I FABP); Mortality; sCD14; T cell activation; Zonulin 1

Indexed keywords

ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT; C REACTIVE PROTEIN; CD14 ANTIGEN; CD38 ANTIGEN; D DIMER; FATTY ACID BINDING PROTEIN 2; HLA DR ANTIGEN; INTERLEUKIN 6; KYNURENINE; PROTEIN; TRYPTOPHAN; TUMOR NECROSIS FACTOR RECEPTOR 1; UNCLASSIFIED DRUG; VIRUS RNA; ZONULIN 1;

ADULT; ARTICLE; BLOOD CLOTTING; CASE CONTROL STUDY; CD4 LYMPHOCYTE COUNT; CD4+ T LYMPHOCYTE; CLINICAL ASSESSMENT; COHORT ANALYSIS; CONTROLLED STUDY; CYTOMEGALOVIRUS RETINITIS; FEMALE; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IMMUNOSTIMULATION; INFLAMMATION; INNATE IMMUNITY; INTESTINE INJURY; INTESTINE MUCOSA PERMEABILITY; MAJOR CLINICAL STUDY; MALE; MORTALITY; NONHUMAN; PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; T LYMPHOCYTE ACTIVATION; ANTIRETROVIRAL THERAPY; CD28; CD38; CD57; CYTOMEGALOVIRUS; D-DIMER; GUT EPITHELIAL CELL BARRIER; HLA-DR; HSCRP; HUMAN IMMUNODEFICIENCY VIRUS; IL-6; IMMUNE ACTIVATION; IMMUNOLOGY; INTESTINAL FATTY ACID BINDING PROTEIN (I-FABP); INTESTINE MUCOSA; LYMPHOCYTE ACTIVATION; METABOLISM; MIDDLE AGED; PATHOPHYSIOLOGY; PHYSIOLOGY; SCD14; T LYMPHOCYTE; T-CELL ACTIVATION; ZONULIN-1;

ANTIRETROVIRAL THERAPY; CD28; CD38; CD57; CYTOMEGALOVIRUS; D-DIMER; GUT EPITHELIAL CELL BARRIER; HIV; HLA-DR; HSCRP; IL-6; IMMUNE ACTIVATION; INTESTINAL FATTY ACID BINDING PROTEIN (I-FABP); MORTALITY; SCD14; T-CELL ACTIVATION; ZONULIN-1;

ADULT; BLOOD COAGULATION; CASE-CONTROL STUDIES; FEMALE; HIV INFECTIONS; HUMANS; IMMUNITY, INNATE; INFLAMMATION; INTESTINAL MUCOSA; LYMPHOCYTE ACTIVATION; MALE; MIDDLE AGED; T-LYMPHOCYTES;

EID: 84902281875     PISSN: 00221899     EISSN: 15376613     Source Type: Journal    
DOI: 10.1093/infdis/jiu238     Document Type: Article

References (49)

1. Hogg R, Lima V, Sterne JAC, et al. Life expectancy of individuals on combination antiretroviral therapy in high-income countries: a collaborative analysis of 14 cohort studies. Lancet 2008;372:293-9.
2. Lohse N, Hansen AB, Pedersen G, et al. Survival of persons with and without HIV infection in Denmark, 1995-2005. Ann Intern Med 2007;146:87-95.
3. Van Sighem AI, Gras LA, Reiss P, Brinkman K, De Wolf F. Life expectancy of recently diagnosed asymptomatic HIV-infected patients approaches that of uninfected individuals. AIDS 2010;24:1527-35.
4. Lewden C, Bouteloup V, De Wit S, et al. All-cause mortality in treated HIV-infected adults with CD4 >/=500/mm3 compared with the general population: evidence from a large European observational cohort collaboration. Int J Epidemiol 2012;41:433-45.
5. Kuller LH, Tracy R, Belloso W, et al. Inflammatory and coagulation biomarkers and mortality in patients with HIV infection. PLoS Med 2008;5:e203.
6. Duprez DA, Kuller LH, Tracy R, et al. Lipoprotein particle subclasses, cardiovascular disease and HIV infection. Atherosclerosis 2009;207:524-9.
7. Tien PC, Choi AI, Zolopa AR, et al. Inflammation and mortality in HIV-infected adults: analysis of the FRAM study cohort. J Acquir Immune Defic Syndr 2010;55:316.
8. Kalayjian RC, Machekano RN, Rizk N, et al. Pretreatment levels of soluble cellular receptors and interleukin-6 are associated with HIV disease progression in subjects treated with highly active antiretroviral therapy. J Infect Dis 2010;201:1796-805.
9. Boulware DR, Hullsiek KH, Puronen CE, et al. Higher levels of CRP, D-dimer, IL-6, and hyaluronic acid before initiation of antiretroviral therapy (ART) are associated with increased risk of AIDS or death. J Infect Dis 2011;203:1637-46.
10. Tenorio A, Zheng E, Bosch R, et al. Soluble markers of inflammation & coagulation, but not T-cell activation, predict non-AIDS-defining events during suppressive antiretroviral therapy [abstract 790]. In: Program and abstracts of the 20th Conference on Retroviruses and Opportunistic Infections, Atlanta, Georgia, 2013.
11. Ledwaba L, Tavel JA, Khabo P, et al. Pre-ART levels of inflammation and coagulation markers are strong predictors of death in a South African cohort with advanced HIV disease. PLoS One 2012;7:e24243.
12. Brown TT, Tassiopoulos K, Bosch RJ, Shikuma C, McComsey GA. Association between systemic inflammation and incident diabetes in HIV-infected patients after initiation of antiretroviral therapy. Diabetes Care 2010;33:2244-9.
13. Triant VA, Meigs JB, Grinspoon SK. Association of C-reactive protein and HIV infection with acute myocardial infarction. J Acquir Immune Defic Syndr 2009;51:268.
14. Ford ES, Greenwald JH, Richterman AG, et al. Traditional risk factors and D-dimer predict incident cardiovascular disease events in chronic HIV infection. AIDS 2010;24:1509-17.
15. Burdo TH, Weiffenbach A, Woods SP, Letendre S, Ellis RJ, Williams KC. Elevated sCD163 is a marker of neurocognitive impairment in HIV infection. AIDS 2013;27:1387-95.
16. Lyons JL, Uno H, Ancuta P, et al. Plasma sCD14 is a biomarker associated with impaired neurocognitive test performance in attention and learning domains in HIV infection. J Acquir Immune Defic Syndr 2011;57:371-9.
17. Letendre S, Marcotte T, Deutsch R, et al. A concise panel of biomarkers diagnoses and predicts neurocognitive status in HIV-infected individuals [abstract 82]. In: Program and abstracts from the 19th Conference on Retroviruses and Opportunistic Infections, Seattle, Washington, 2012.
18. Sandler NG, Wand H, Roque A, et al. Plasma levels of soluble CD14 independently predict mortality in HIV infection. J Infect Dis 2011;203:780-90.
19. Justice AC, Freiberg MS, Tracy R, et al. Does an index composed of clinical data reflect effects of inflammation, coagulation, and monocyte activation on mortality among those aging with HIV? Clin Infect Dis 2012;54:984-94.
20. Vujkovic-Cvijin I, Dunham RM, Iwai S, et al. Dysbiosis of the gut microbiota is associated with HIV disease progression and tryptophan catabolism. Sci Transl Med 2013;5:193ra91.
21. Boasso A, Herbeuval JP, Hardy AW, et al. HIV inhibits CD4+ T-cell proliferation by inducing indoleamine 2, 3-dioxygenase in plasmacytoid dendritic cells. Blood 2007;109:3351-9.
22. Favre D, Mold J, Hunt PW, et al. Tryptophan catabolism by indoleamine 2, 3-dioxygenase 1 alters the balance of TH17 to regulatory T cells in HIV disease. Sci Transl Med 2010;2:32ra36.
23. Byakwaga H, Boum Y II, Huang Y, et al. The kynurenine pathway of tryptophan catabolism, CD4+ T-cell recovery and mortality in HIV-infected Ugandans initiating antiretroviral therapy. J Infect Dis 2014;210:383-91.
24. Giorgi JV, Hultin LE, McKeating JA, et al. Shorter survival in advanced human immunodeficiency virus type 1 infection is more closely associated with T lymphocyte activation than with plasma virus burden or virus chemokine coreceptor usage. J Infect Dis 1999;179:859-70.
25. Giorgi JV, Lyles RH, Matud JL, et al. Predictive value of immunologic and virologic markers after long or short duration of HIV-1 infection. J Acquir Immune Defic Syndr 2002;29:346-55.
26. Wikby A, Johansson B, Olsson J, Lofgren S, Nilsson BO, Ferguson F. Expansions of peripheral blood CD8 T-lymphocyte subpopulations and an association with cytomegalovirus seropositivity in the elderly: the Swedish NONA immune study. Exp Gerontol 2002;37:445-53.
27. Lee SA, Sinclair E, Jain V, et al. Low proportions of CD28-CD8+ T cells expressing CD57 can be reversed by early ART initiation and predict mortality in treated HIV infection. J Infect Dis 2014;210:374-82.
28. Hatano H, Jain V, Hunt PW, et al. Cell-based measures of viral persistence are associated with immune activation and programmed cell death protein 1 (PD-1)-expressing CD4+ T cells. J Infect Dis 2013;208:50-6.
29. Hatano H, Scherzer R, Wu Y, et al. A randomized controlled trial assessing the effects of raltegravir intensification on endothelial function in treated HIV infection. J Acquir Immune Defic Syndr 2012;61:317-25.
30. Huang Y, Louie A, Yang Q, et al. A simple LC-MS/MS method for determination of kynurenine and tryptophan concentrations in human plasma from HIV-infected patients. Bioanalysis 2013;5:1397-407.
31. Fasano A. Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer. Physiol Rev 2011;91:151-75.
32. Hunt PW, Cao HL, Muzoora C, et al. Impact of CD8+ T-cell activation on CD4+ T-cell recovery and mortality in HIV-infected Ugandans initiating antiretroviral therapy. AIDS 2011;25:2123-31.
33. Brenchley JM, Price DA, Schacker TW, et al. Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nat Med 2006;12:1365-71.
34. Burdo TH, Lentz MR, Autissier P, et al. Soluble CD163 made by monocyte/macrophages is a novel marker of HIV activity in early and chronic infection prior to and after anti-retroviral therapy. J Infect Dis 2011;204:154-63.
35. Jain V, Hartogensis W, Bacchetti P, et al. Antiretroviral therapy initiated within six months of HIV infection is associated with lower T-cell activation and smaller HIV reservoir size. J Infect Dis 2013;208:1202-11.
36. Vinikoor M, Cope A, Gay C, et al. ART started during acute HIV infection failed to prevent persistent immune activation [abstract 554]. In: Program and abstracts of the 19th Conference on Retroviruses and Opportunistic Infections, Seattle, Washington, 2012.
37. Gandhi RT, Spritzler J, Chan E, et al. Effect of baseline- and treatmentrelated factors on immunologic recovery after initiation of antiretroviral therapy in HIV-1-positive subjects: results from ACTG 384. J Acquir Immune Defic Syndr 2006;42:426-34.
38. Goicoechea M, Smith DM, Liu L, et al. Determinants of CD4+ T cell recovery during suppressive antiretroviral therapy: association of immune activation, T cell maturation markers, and cellular HIV-1 DNA. J Infect Dis 2006;194:29-37.
39. Hunt PW, Martin JN, Sinclair E, et al. T cell activation is associated with lower CD4+ T cell gains in human immunodeficiency virus-infected patients with sustained viral suppression during antiretroviral therapy. J Infect Dis 2003;187:1534-43.
40. Zhang X, Hunt PW, Hammer SM, Cespedes MS, Patterson KB, Bosch RJ. Immune activation while on potent antiretroviral therapy can predict subsequent CD4+ T-cell increases through 15 years of treatment. HIV Clin Trials 2013;14:61-7.
41. Lok J, Hunt P, Collier A, et al. The impact of age on the prognostic capacity of CD8+ T-cell activation during suppressive antiretroviral therapy. AIDS 2013;27:2101-10.
42. Hunt PW, Shulman NS, Hayes TL, et al. The immunologic effects of maraviroc intensification in treated HIV-infected individuals with incomplete CD4+ T-cell recovery: a randomized trial. Blood 2013;121:4635-46.
43. Read SW, De Grezia M, Ciccone EJ, et al. The effect of leflunomide on cycling and activation of T-cells in HIV-1-infected participants. PLoS One 2010;5:e11937.
44. Hunt PW, Martin JN, Sinclair E, et al. Valganciclovir reduces T cell activation in HIV-infected individuals with incomplete CD4+ T cell recovery on antiretroviral therapy. J Infect Dis 2011;203:1474-83.
45. Hadrup SR, Strindhall J, Kollgaard T, et al. Longitudinal studies of clonally expanded CD8 T cells reveal a repertoire shrinkage predicting mortality and an increased number of dysfunctional cytomegalovirusspecific T cells in the very elderly. J Immunol 2006;176:2645-53.
46. Almanzar G, Schwaiger S, Jenewein B, et al. Long-term cytomegalovirus infection leads to significant changes in the composition of the CD8+ T-cell repertoire, which may be the basis for an imbalance in the cytokine production profile in elderly persons. J Virol 2005;79:3675-83.
47. Vescovini R, Biasini C, Telera AR, et al. Intense antiextracellular adaptive immune response to human cytomegalovirus in very old subjects with impaired health and cognitive and functional status. J Immunol 2010;184:3242-9.
48. Deayton JR, Sabin CA, Johnson MA, Emery VC, Wilson P, Griffiths PD. Importance of cytomegalovirus viraemia in risk of disease progression and death in HIV-infected patients receiving highly active antiretroviral therapy. Lancet 2004;363:2116-21.
49. El Amari EB, Combescure C, Yerly S, et al. Clinical relevance of cytomegalovirus viraemia. HIV Med 2011;12:394-402.