Dynamics of immune reconstitution and activation markers in HIV+ treatment-naïve patients treated with raltegravir, tenofovir disoproxil fumarate and emtricitabine

PLoS ONE

Volumn 8, Issue 12, 2013, Pages

  Funderburg, Nicholas T ^a   Andrade, Adriana ^b   Chan, Ellen S ^c   Rosenkranz, Susan L ^c   Lu, Darlene ^c   Clagett, Brian ^a   Pilch Cooper, Heather A ^a   Rodriguez, Benigno ^a   Feinberg, Judith ^d   Daar, Eric ^e   Mellors, John ^f   Kuritzkes, Daniel ^g   Jacobson, Jeffrey M ^h   Lederman, Michael M ^a  

^a CASE WESTERN RESERVE UNIVERSITY   (United States)

^b JOHNS HOPKINS UNIVERSITY   (United States)

^c CENTER FOR BIOSTATISTICS IN AIDS RESEARCH   (United States)

^d UNIVERSITY OF CINCINNATI MEDICAL CENTER   (United States)

^e HARBOR UCLA MEDICAL CENTER   (United States)

^f UNIVERSITY OF PITTSBURGH MEDICAL CENTER   (United States)

^g BRIGHAM AND WOMEN S HOSPITAL   (United States)

^h DREXEL UNIVERSITY COLLEGE OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

D DIMER; EMTRICITABINE PLUS TENOFOVIR DISOPROXIL; INTERLEUKIN 6; RALTEGRAVIR; TUMOR NECROSIS FACTOR RECEPTOR 1;

ADULT; ARTICLE; CD4 LYMPHOCYTE COUNT; CD4+ CD8+ T LYMPHOCYTE; CD4+ T LYMPHOCYTE; CELL CYCLE; CELL REGENERATION; CLINICAL ARTICLE; CONTROLLED STUDY; FEMALE; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; IMMUNOREACTIVITY; INFLAMMATION; MALE; T LYMPHOCYTE; T LYMPHOCYTE ACTIVATION; T LYMPHOCYTE SUBPOPULATION; VIROLOGY; VIRUS REPLICATION;

ADENINE; ADULT; ANTI-HIV AGENTS; BIOLOGICAL MARKERS; CD4 LYMPHOCYTE COUNT; CD4-POSITIVE T-LYMPHOCYTES; DEOXYCYTIDINE; FEMALE; HIV INFECTIONS; HIV-1; HUMANS; LYMPHOCYTE ACTIVATION; MALE; MIDDLE AGED; ORGANOPHOSPHONATES; PYRROLIDINONES; YOUNG ADULT;

EID: 84893171544     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0083514     Document Type: Article

References (41)

1. Brenchley JM, Schacker TW, Ruff LE, Price DA, Taylor JH et al. (2004) CD4+ T cell depletion during all stages of HIV disease occurs predominantly in the gastrointestinal tract. J Exp Med 200: 749-759. doi:10.1084/jem.20040874. PubMed: 15365096. (Pubitemid 39299461)
2. Giorgi JV, Hultin LE, McKeating JA, Johnson TD, Owens B et al. (1999) 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 179: 859-870. doi:10.1086/314660. PubMed: 10068581. (Pubitemid 29159331)
3. Hunt PW, Martin JN, Sinclair E, Bredt B, Hagos E et al. (2003) 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 187: 1534-1543. doi:10.1086/374786. PubMed: 12721933. (Pubitemid 36578959)
4. Anthony KB, Yoder C, Metcalf JA, DerSimonian R, Orenstein JM et al. (2003) Incomplete CD4 T cell recovery in HIV-1 infection after 12 months of highly active antiretroviral therapy is associated with ongoing increased CD4 T cell activation and turnover. J Acquir Immune Defic Syndr 33: 125-133. doi:10.1097/00126334-200306010-00002. PubMed: 12794543. (Pubitemid 36793144)
5. Heil F, Hemmi H, Hochrein H, Ampenberger F, Kirschning C et al. (2004) Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8. Science 303: 1526-1529. doi:10.1126/science.1093620. PubMed: 14976262. (Pubitemid 38314424)
6. Meier A, Alter G, Frahm N, Sidhu H, Li B et al. (2007) MyD88-dependent immune activation mediated by human immunodeficiency virus type 1-encoded toll-like receptor ligands. J Virol 81: 8180-8191. doi:10.1128/JVI.00421-07. PubMed: 17507480. (Pubitemid 47101504)
7. Beignon AS, McKenna K, Skoberne M, Manches O, DaSilva I et al. (2005) Endocytosis of HIV-1 activates plasmacytoid dendritic cells via Toll-like receptor-viral RNA interactions. J Clin Invest 115: 3265-3275. doi:10.1172/JCI26032. PubMed: 16224540. (Pubitemid 41567591)
8. Hunt PW, Martin JN, Sinclair E, Epling L, Teague J et al. (2011) Valganciclovir reduces T cell activation in HIV-infected individuals with incomplete CD4+ T cell recovery on antiretroviral therapy. J Infect Dis 203: 1474-1483. doi:10.1093/infdis/jir060. PubMed: 21502083.
9. Brenchley JM, Price DA, Schacker TW, Asher TE, Silvestri G et al. (2006) Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nat Med, 12: 1365-71. PubMed: 17115046. (Pubitemid 44924494)
10. Jiang W, Lederman MM, Hunt P, Sieg SF, Haley K et al. (2009) Plasma levels of bacterial DNA correlate with immune activation and the magnitude of immune restoration in persons with antiretroviral-treated HIV infection. J Infect Dis 199: 1177-1185. doi:10.1086/597476. PubMed: 19265479.
11. Marchetti G, Bellistrì GM, Borghi E, Tincati C, Ferramosca S et al. (2008) Microbial translocation is associated with sustained failure in CD4+ T-cell reconstitution in HIV-infected patients on long-term highly active antiretroviral therapy. AIDS 22: 2035-2038. doi:10.1097/QAD.0b013e3283112d29. PubMed: 18784466.
12. Klatt NR, Funderburg NT, Brenchley JM (2013) Microbial translocation, immune activation, and HIV disease. Trends Microbiol 21: 6-13. doi:10.1016/j.tim.2012.09.001. PubMed: 23062765.
13. Bucy RP, Hockett RD, Derdeyn CA, Saag MS, Squires K et al. (1999) Initial increase in blood CD4(+) lymphocytes after HIV antiretroviral therapy reflects redistribution from lymphoid tissues. J Clin Invest 103: 1391-1398. doi:10.1172/JCI5863. PubMed: 10330421. (Pubitemid 29535495)
14. Pakker NG, Notermans DW, de Boer RJ, Roos MT, de Wolf F et al. (1998) Biphasic kinetics of peripheral blood T cells after triple combination therapy in HIV-1 infection: a composite of redistribution and proliferation. Nat Med 4: 208-214. doi:10.1038/nm0298-208. PubMed: 9461195. (Pubitemid 28137376)
15. Funderburg N, Luciano AA, Jiang W, Rodriguez B, Sieg SF et al. (2008) Toll-like receptor ligands induce human T cell activation and death, a model for HIV pathogenesis. PLOS ONE 3: e1915. doi:10.1371/journal.pone.0001915. PubMed: 18382686.
16. Autran B, Carcelain G, Li TS, Blanc C, Mathez D et al. (1997) Positive effects of combined antiretroviral therapy on CD4+ T cell homeostasis and function in advanced HIV disease. Science 277: 112-116. doi:10.1126/science.277. 5322.112. PubMed: 9204894. (Pubitemid 27450659)
17. Lederman MM, Connick E, Landay A, Kuritzkes DR, Spritzler J, et al. (1998) Immunologic responses associated with 12 weeks of combination antiretroviral therapy consisting of zidovudine, lamivudine, and ritonavir: results of AIDS Clinical Trials Group Protocol 315. J Infect Dis 178: 70-79. (Pubitemid 28328078)
18. Gandhi RT, Spritzler J, Chan E, Asmuth DM, Rodriguez B et al. (2006) Effect of baseline- and treatment-related factors on immunologic recovery after initiation of antiretroviral therapy in HIV-1-positive subjects: results from ACTG 384. J Acquir Immune Defic Syndr 42: 426-434. doi:10.1097/01.qai. 0000226789.51992.3f. PubMed: 16810109. (Pubitemid 44050889)
19. Andrade A, Rosenkranz SL, Cillo AR, Lu D, Daar ES et al. (2013) Three Distinct Phases of HIV-1 RNA Decay in Treatment-Naïve Patients Receiving Raltegravir-Based Antiretroviral Therapy: ACTG A5248 Study Journal of Infectious Diseases in Press.
20. Funderburg NT, Zidar DA, Shive C, Lioi A, Mudd J et al. (2012) Shared monocyte subset phenotypes in HIV-1 infection and in uninfected subjects with acute coronary syndromes. Blood.
21. Lederman MM, Calabrese L, Funderburg NT, Clagett B, Medvik K et al. (2011) Immunologic failure despite suppressive antiretroviral therapy is related to activation and turnover of memory CD4 cells. J Infect Dis 204: 1217-1226. doi:10.1093/infdis/jir507. PubMed: 21917895.
22. Lederman MM, McKinnis R, Kelleher D, Cutrell A, Mellors J et al. (2000) Cellular restoration in HIV infected persons treated with abacavir and a protease inhibitor: age inversely predicts naive CD4 cell count increase. AIDS 14: 2635-2642. doi:10.1097/00002030-200012010-00002. PubMed: 11125881. (Pubitemid 32118716)
23. Schacker TW, Bosch RJ, Bennett K, Pollard R, Robbins GK et al. (2010) Measurement of naive CD4 cells reliably predicts potential for immune reconstitution in HIV. J Acquir Immune Defic Syndr 54: 59-62. PubMed: 20182359.
24. Okoye A, Meier-Schellersheim M, Brenchley JM, Hagen SI, Walker JM et al. (2007) Progressive CD4+ central memory T cell decline results in CD4+ effector memory insufficiency and overt disease in chronic SIV infection. J Exp Med 204: 2171-2185. doi:10.1084/jem.20070567. PubMed: 17724130. (Pubitemid 47360877)
25. Sieg SF, Rodriguez B, Asaad R, Jiang W, Bazdar DA et al. (2005) Peripheral S-phase T cells in HIV disease have a central memory phenotype and rarely have evidence of recent T cell receptor engagement. J Infect Dis 192: 62-70. doi:10.1086/430620. PubMed: 15942895. (Pubitemid 40863858)
26. Picker LJ, Hagen SI, Lum R, Reed-Inderbitzin EF, Daly LM et al. (2004) Insufficient production and tissue delivery of CD4+ memory T cells in rapidly progressive simian immunodeficiency virus infection. J Exp Med 200: 1299-1314. doi:10.1084/jem.20041049. PubMed: 15545355. (Pubitemid 39552571)
27. Funderburg NT, Mayne E, Sieg SF, Asaad R, Jiang W et al. (2010) Increased tissue factor expression on circulating monocytes in chronic HIV infection: relationship to in vivo coagulation and immune activation. Blood 115: 161-167. doi:10.1182/blood-2009-03-210179. PubMed: 19828697.
28. Kuller LH, Tracy R, Belloso W, De Wit S, Drummond F et al. (2008) Inflammatory and coagulation biomarkers and mortality in patients with HIV infection. PLoS Med 5: e203. doi:10.1371/journal.pmed.0050203. PubMed: 18942885.
29. Musselwhite LW, Sheikh V, Norton TD, Rupert A, Porter BO et al. (2011) Markers of endothelial dysfunction, coagulation and tissue fibrosis independently predict venous thromboembolism in HIV. AIDS 25: 787-795. doi:10.1097/QAD.0b013e3283453fcb. PubMed: 21412059.
30. Hunt PW, Rodriguez B, Shive C, Clagett B, Funderburg N et al. (2012) Gut Epithelial Barrier Dysfunction, Inflammation and Coagulation Predict Higher Mortality during Treated HIV/AIDS. CROI. Seattle, Washington.
31. Kalayjian RC, Machekano RN, Rizk N, Robbins GK, Gandhi RT et al. (2010) 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 201: 1796-1805. doi:10.1086/652750. PubMed: 20446847.
32. Gray CM, Lawrence J, Schapiro JM, Altman JD, Winters MA et al. (1999) Frequency of class I HLA-restricted anti-HIV CD8+ T cells in individuals receiving highly active antiretroviral therapy (HAART). J Immunol 162: 1780-1788. PubMed: 9973442. (Pubitemid 29307058)
33. Kalams SA, Goulder PJ, Shea AK, Jones NG, Trocha AK et al. (1999) Levels of human immunodeficiency virus type 1-specific cytotoxic T-lymphocyte effector and memory responses decline after suppression of viremia with highly active antiretroviral therapy. J Virol 73: 6721-6728. PubMed: 10400770. (Pubitemid 29327855)
34. Bosch RJ, Wang R, Vaida F, Lederman MM, Albrecht MA (2006) Changes in the slope of the CD4 cell count increase after initiation of potent antiretroviral treatment. J Acquir Immune Defic Syndr 43: 433-435. doi:10.1097/01.qai. 0000243097.27029.b7. PubMed: 17183628. (Pubitemid 44737100)
35. Di Mascio M, Sereti I, Matthews LT, Natarajan V, Adelsberger J et al. (2006) Naive T-cell dynamics in human immunodeficiency virus type 1 infection: effects of highly active antiretroviral therapy provide insights into the mechanisms of naive T-cell depletion. J Virol 80: 2665-2674. doi:10.1128/JVI.80.6.2665-2674.2006. PubMed: 16501076. (Pubitemid 43346362)
36. Srinivasula S, Lempicki RA, Adelsberger JW, Huang CY, Roark J et al. (2011) Differential effects of HIV viral load and CD4 count on proliferation of naive and memory CD4 and CD8 T lymphocytes. Blood 118: 262-270. doi:10.1182/blood-2011-02-335174. PubMed: 21562041.
37. Ciccone EJ, Read SW, Mannon PJ, Yao MD, Hodge JN et al. (2010) Cycling of gut mucosal CD4+ T cells decreases after prolonged antiretroviral therapy and is associated with plasma LPS levels. Mucosal Immunol 3: 172-181. doi:10.1038/mi.2009.129. PubMed: 19956090.
38. Shive CL, Funderburg NT, Mudd JC, Sieg SF, D.A. B et al. (2013) Acute phase cytokine down-regulates IL-7Rα and induces CD4 T cell cycling without proliferation or induction of the survival factor Bcl2. Keystone Conference on Immune Activation in HIV Infection: Basic Mechanisms and Clinical Implications. Breckenridge CO. U.S.A.
39. Estes J, Baker JV, Brenchley JM, Khoruts A, Barthold JL et al. (2008) Collagen deposition limits immune reconstitution in the gut. J Infect Dis 198: 456-464. doi:10.1086/590112. PubMed: 18598193.
40. Bas S, Gauthier BR, Spenato U, Stingelin S, Gabay C (2004) CD14 is an acute-phase protein. J Immunol 172: 4470-4479. PubMed: 15034063. (Pubitemid 38375263)
41. Sandler NG, Wand H, Roque A, Law M, Nason MC et al. (2011) Plasma levels of soluble CD14 independently predict mortality in HIV infection. J Infect Dis 203: 780-790. doi:10.1093/infdis/jiq118. PubMed: 21252259.