Treatment intensification with maraviroc (CCR5 antagonist) leads to declines in CD16-expressing monocytes in cART-suppressed chronic HIV-infected subjects and is associated with improvements in neurocognitive test performance: implications for HIV-associated neurocognitive disease (HAND)

Journal of NeuroVirology

Volumn 20, Issue 6, 2014, Pages 571-582

  Ndhlovu, Lishomwa C ^a   Umaki, Tracie ^a   Chew, Glen M ^a   Chow, Dominic C ^a   Agsalda, Melissa ^a   Kallianpur, Kalpana J ^a   Paul, Robert ^b   Zhang, Guangxiang ^a   Ho, Erika ^a   Hanks, Nancy ^a   Nakamoto, Beau ^a   Shiramizu, Bruce T ^a   Shikuma, Cecilia M ^a  

^a UNIVERSITY OF HAWAII   (United States)

^b UNIVERSITY OF MISSOURI ST LOUIS   (United States)

Author keywords

CCR5; CD163; DNA; HIV; HIV associated neurocognitive disorders; Inflammation; Monocytes

Indexed keywords

ANTIRETROVIRUS AGENT; CD16 ANTIGEN; MARAVIROC; ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT; CCR5 PROTEIN, HUMAN; CHEMOKINE RECEPTOR CCR5; CYCLOHEXANE DERIVATIVE; FC RECEPTOR; FCGR3B PROTEIN, HUMAN; GLYCOSYLPHOSPHATIDYLINOSITOL ANCHORED PROTEIN; TRIAZOLE DERIVATIVE;

ADULT; AGED; ARTICLE; CD8+ T LYMPHOCYTE; CLINICAL ARTICLE; COGNITIVE DEFECT; CONTROLLED STUDY; DNA CONTENT; FEMALE; FLOW CYTOMETRY; FOLLOW UP; HIV ASSOCIATED DEMENTIA; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS INFECTED PATIENT; INFLAMMATION; MALE; MONOCYTE; NEUROPSYCHOLOGICAL TEST; POLYMERASE CHAIN REACTION; T LYMPHOCYTE ACTIVATION; ACQUIRED IMMUNODEFICIENCY SYNDROME; AIDS DEMENTIA COMPLEX; COGNITION; DISEASE MANAGEMENT; DRUG EFFECTS; GENE EXPRESSION; GENETICS; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HUMAN IMMUNODEFICIENCY VIRUS 1; LEUKOCYTE COUNT; METABOLISM; MIDDLE AGED; PATHOLOGY; PATHOPHYSIOLOGY; PHYSIOLOGY; VIROLOGY; VIRUS LOAD;

ACQUIRED IMMUNODEFICIENCY SYNDROME; AGED; AIDS DEMENTIA COMPLEX; ANTI-HIV AGENTS; ANTIRETROVIRAL THERAPY, HIGHLY ACTIVE; COGNITION; CYCLOHEXANES; DISEASE MANAGEMENT; FEMALE; GENE EXPRESSION; GPI-LINKED PROTEINS; HIV-1; HUMANS; LEUKOCYTE COUNT; MALE; MIDDLE AGED; MONOCYTES; NEUROPSYCHOLOGICAL TESTS; RECEPTORS, CCR5; RECEPTORS, IGG; TRIAZOLES; VIRAL LOAD;

EID: 84916596091     PISSN: 13550284     EISSN: 15382443     Source Type: Journal    
DOI: 10.1007/s13365-014-0279-x     Document Type: Article

References (69)

1. Abdulle S, Hagberg L, Svennerholm B, Fuchs D, Gisslen M (2002) Continuing intrathecal immunoactivation despite two years of effective antiretroviral therapy against HIV-1 infection. AIDS 16:2145–2149
2. Abeles RD, McPhail MJ, Sowter D, Antoniades CG, Vergis N, Vijay GK, Xystrakis E, Khamri W, Shawcross DL, Ma Y, Wendon JA, Vergani D (2012) CD14, CD16 and HLA-DR reliably identifies human monocytes and their subsets in the context of pathologically reduced HLA-DR expression by CD14(hi)/CD16(neg) monocytes: expansion of CD14(hi)/CD16(pos) and contraction of CD14(lo)/CD16(pos) monocytes in acute liver failure. Cytometry A 81:823–834
3. Alkhatib G, Combadiere C, Broder CC, Feng Y, Kennedy PE, Murphy PM, Berger EA (1996) A RANTES, MIP-1alpha, MIP-1beta receptor as a fusion cofactor for macrophage-tropic HIV-1. Science 272:1955–1958
4. Andrade AS, Deutsch R, AC S, Duarte NA, Marcotte TD, Umlauf A, Atkinson JH, McCutchan JA, Franklin D, Alexander TJ, McArthur JC, Marra C, Grant I, Collier AC (2013) Relationships among neurocognitive status, medication adherence measured by pharmacy refill records, and virologic suppression in HIV-infected persons. J Acquir Immune Defic Syndr 62:282–92
5. Anthony IC, Ramage SN, Carnie FW, Simmonds P, Bell JE (2005) Influence of HAART on HIV-related CNS disease and neuroinflammation. J Neuropathol Exp Neurol 64:529–536
6. Aquaro S, Svicher V, Schols D, Pollicita M, Antinori A, Balzarini J, Perno CF (2006) Mechanisms underlying activity of antiretroviral drugs in HIV-1-infected macrophages: new therapeutic strategies. J Leukoc Biol 80:1103–1110
7. Barbour JD, Jalbert EC, Chow DC, Gangcuangco LM, Norris PJ, Keating SM, Heitman J, Nagamine L, Seto T, Ndhlovu LC, Nakamoto BK, Hodis HN, Parikh NI, Shikuma CM (2014) Reduced CD14 expression on classical monocytes and vascular endothelial adhesion markers independently associate with carotid artery intima media thickness in chronically HIV-1 infected adults on virologically suppressive anti-retroviral therapy. Atherosclerosis 232:52–58
8. Beck ATWC, Mendelson M (1961) Beck Depression Inventory (BDI). Arch Gen Psychiatry 4(6):561–571
9. Benedict RH, Mezhir JJ, Walsh K, Hewitt RG (2000) Impact of human immunodeficiency virus type-1-associated cognitive dysfunction on activities of daily living and quality of life. Arch Clin Neuropsychol 15:535–544
10. Burdo TH, Soulas C, Orzechowski K, Button J, Krishnan A, Sugimoto C, Alvarez X, Kuroda MJ, Williams KC (2010) Increased monocyte turnover from bone marrow correlates with severity of SIV encephalitis and CD163 levels in plasma. PLoS Pathog 6:e1000842
11. Burdo TH, Lentz MR, Autissier P, Krishnan A, Halpern E, Letendre S, Rosenberg ES, Ellis RJ, Williams KC (2011) 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 204:154–163
12. Burdo TH, Weiffenbach A, Woods SP, Letendre S, Ellis RJ, Williams KC (2013) Elevated sCD163 in plasma but not cerebrospinal fluid is a marker of neurocognitive impairment in HIV infection. Aids 27:1387–1395
13. Clinical confirmation of the American Academy of Neurology algorithm for HIV-1-associated cognitive/motor disorder (1996) The Dana Consortium on Therapy for HIV Dementia and Related Cognitive Disorders. Neurology 47:1247–1253
14. Crawford TQ, Ndhlovu LC, Tan A, Carvidi A, Hecht FM, Sinclair E, Barbour JD (2011) HIV-1 infection abrogates CD8+ T cell mitogen-activated protein kinase signaling responses. J Virol 85:12343–12350
15. Cysique LA, Maruff P, Brew BJ (2004) Prevalence and pattern of neuropsychological impairment in human immunodeficiency virus-infected/acquired immunodeficiency syndrome (HIV/AIDS) patients across pre- and post-highly active antiretroviral therapy eras: a combined study of two cohorts. J Neurovirol 10:350–357
16. Cysique LA, Vaida F, Letendre S, Gibson S, Cherner M, Woods SP, McCutchan JA, Heaton RK, Ellis RJ (2009) Dynamics of cognitive change in impaired HIV-positive patients initiating antiretroviral therapy. Neurology 73:342–348
17. Deng H, Liu R, Ellmeier W, Choe S, Unutmaz D, Burkhart M, Di Marzio P, Marmon S, Sutton RE, Hill CM, Davis CB, Peiper SC, Schall TJ, Littman DR, Landau NR (1996) Identification of a major co-receptor for primary isolates of HIV-1. Nature 381:661–666
18. Dinoso JB, Kim SY, Wiegand AM, Palmer SE, Gange SJ, Cranmer L, O'Shea A, Callender M, Spivak A, Brennan T, Kearney MF, Proschan MA, Mican JM, Rehm CA, Coffin JM, Mellors JW, Siliciano RF, Maldarelli F (2009) Treatment intensification does not reduce residual HIV-1 viremia in patients on highly active antiretroviral therapy. Proc Natl Acad Sci U S A 106:9403–9408
19. Droste A, Sorg C, Hogger P (1999) Shedding of CD163, a novel regulatory mechanism for a member of the scavenger receptor cysteine-rich family. Biochem Biophys Res Commun 256:110–113
20. Eden A, Price RW, Spudich S, Fuchs D, Hagberg L, Gisslen M (2007) Immune activation of the central nervous system is still present after >4 years of effective highly active antiretroviral therapy. J Infect Dis 196:1779–1783
21. Farina C, Theil D, Semlinger B, Hohlfeld R, Meinl E (2004) Distinct responses of monocytes to toll-like receptor ligands and inflammatory cytokines. Int Immunol 16:799–809
22. Funderburg N, Kalinowska M, Eason J, Goodrich J, Heera J, Mayer H, Rajicic N, Valdez H, Lederman MM (2010) Effects of maraviroc and efavirenz on markers of immune activation and inflammation and associations with CD4+ cell rises in HIV-infected patients. PLoS One 5:e13188
23. Gartner S (2000) HIV infection and dementia. Science 287:602–604
24. Giancola ML, Lorenzini P, Balestra P, Larussa D, Baldini F, Corpolongo A, Narciso P, Bellagamba R, Tozzi V, Antinori A (2006) Neuroactive antiretroviral drugs do not influence neurocognitive performance in less advanced HIV-infected patients responding to highly active antiretroviral therapy. J Acquir Immune Defic Syndr 41:332–337
25. Gonzalez-Scarano F, Martin-Garcia J (2005) The neuropathogenesis of AIDS. Nat Rev Immunol 5:69–81
26. Gorman AA, Foley JM, Ettenhofer ML, Hinkin CH, van Gorp WG (2009) Functional consequences of HIV-associated neuropsychological impairment. Neuropsychol Rev 19:186–203
27. Gutierrez C DL, Hernandez-Novoa B, et al. (2010). Effect of the intensification with a CCR5 antagonist on the decay of the HIV-1 latent reservoir and residual viremia. In: 17th Conference on Retroviruses and Opportunistic Infections: San Francisco, CA.
28. Harezlak J, Buchthal S, Taylor M, Schifitto G, Zhong J, Daar E, Alger J, Singer E, Campbell T, Yiannoutsos C, Cohen R, Navia B (2011) Persistence of HIV-associated cognitive impairment, inflammation, and neuronal injury in era of highly active antiretroviral treatment. Aids 25:625–633
29. Havlir DV (2003) Strategic approaches to antiretroviral treatment. Top HIV Med 11:145–149
30. Heaton RK, Clifford DB, Franklin DR Jr, Woods SP, Ake C, Vaida F, Ellis RJ, Letendre SL, Marcotte TD, Atkinson JH, Rivera-Mindt M, Vigil OR, Taylor MJ, Collier AC, Marra CM, Gelman BB, McArthur JC, Morgello S, Simpson DM, McCutchan JA, Abramson I, Gamst A, Fennema-Notestine C, Jernigan TL, Wong J, Grant I (2010) HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy: CHARTER study. Neurology 75:2087–2096
31. Hunt PW SN, Hayes T, Dahl V, Somsouk M, Funderburg N, Landay AL, Adeyemi O, Shafer R, Clagett B, Rodriquez B, Martin JN, Shacklett B, Palmer S, Lederman MM, Deeks SG (2011). The immunomodulatory effects of Maraviroc intensification among ART-suppressed patients with incomplete CD4 recovery. Conference on Retroviruses and Opportunistic Infections: Boston, MA
32. Jalbert E, Crawford TQ, D'Antoni ML, Keating SM, Norris PJ, Nakamoto BK, Seto T, Parikh NI, Shikuma CM, Ndhlovu LC, Barbour JD (2013) IL-1beta enriched monocytes mount massive IL-6 responses to common inflammatory triggers among chronically HIV-1 infected adults on stable anti-retroviral therapy at risk for cardiovascular disease. PLoS One 8:e75500
33. Kallianpur KJ, Kirk GR, Sailasuta N, Valcour V, Shiramizu B, Nakamoto BK, Shikuma C (2012) Regional cortical thinning associated with detectable levels of HIV DNA. Cereb Cortex 22:2065–2075
34. Kallianpur KJ, Shikuma C, Kirk GR, Shiramizu B, Valcour V, Chow D, Souza S, Nakamoto B, Sailasuta N (2013) Peripheral blood HIV DNA is associated with atrophy of cerebellar and subcortical gray matter. Neurology 80:1792–1799
35. Kelly KM, Beck SE, Pate KA, Queen SE, Dorsey JL, Adams RJ, Avery LB, Hubbard W, Tarwater PM, Mankowski JL (2013). Neuroprotective maraviroc monotherapy in simian immunodeficiency virus-infected macaques: reduced replicating and latent SIV in the brain. Aids
36. Koenig S, Gendelman HE, Orenstein JM, Dal Canto MC, Pezeshkpour GH, Yungbluth M, Janotta F, Aksamit A, Martin MA, Fauci AS (1986) Detection of AIDS virus in macrophages in brain tissue from AIDS patients with encephalopathy. Science 233:1089–1093
37. Kusao I, Shiramizu B, Liang CY, Grove J, Agsalda M, Troelstrup D, Velasco VN, Marshall A, Whitenack N, Shikuma C, Valcour V (2012) Cognitive performance related to HIV-1-infected monocytes. J Neuropsychiatry Clin Neurosci 24:71–80
38. Leavy O (2011) Immunotherapy: stopping monocytes in their tracks. Nat Rev Immunol 11:715
39. Letendre S, Marquie-Beck J, Capparelli E, Best B, Clifford D, Collier AC, Gelman BB, McArthur JC, McCutchan JA, Morgello S, Simpson D, Grant I, Ellis RJ (2008) Validation of the CNS penetration-effectiveness rank for quantifying antiretroviral penetration into the central nervous system. Arch Neurol 65:65–70
40. McElrath MJ, Pruett JE, Cohn ZA (1989) Mononuclear phagocytes of blood and bone marrow: comparative roles as viral reservoirs in human immunodeficiency virus type 1 infections. Proc Natl Acad Sci U S A 86:675–679
41. Meanwell NA, Kadow JF (2007) Maraviroc, a chemokine CCR5 receptor antagonist for the treatment of HIV infection and AIDS. Curr Opin Investig Drugs 8:669–681
42. Nakasujja N, Miyahara S, Evans S, Lee A, Musisi S, Katabira E, Robertson K, Ronald A, Clifford DB, Sacktor N (2013) Randomized trial of minocycline in the treatment of HIV-associated cognitive impairment. Neurology 80:196–202
43. Psomas C, Lavigne JP, Barbuat C, Trabelsi S, Ghosn J, Lascoux-Combe C, Flandre P, Cuzin L, Reynes J, Autran B, Corbeau P (2013) Maraviroc-induced decrease in circulating bacterial products is not linked to an increase in immune activation in HIV-infected individuals. Blood 122:2282–2283
44. Pulliam L, Gascon R, Stubblebine M, McGuire D, McGrath MS (1997) Unique monocyte subset in patients with AIDS dementia. Lancet 349:692–695
45. Pulliam L, Sun B, Rempel H (2004) Invasive chronic inflammatory monocyte phenotype in subjects with high HIV-1 viral load. J Neuroimmunol 157:93–98
46. Reshef R, Luger SM, Hexner EO, Loren AW, Frey NV, Nasta SD, Goldstein SC, Stadtmauer EA, Smith J, Bailey S, Mick R, Heitjan DF, Emerson SG, Hoxie JA, Vonderheide RH, Porter DL (2012) Blockade of lymphocyte chemotaxis in visceral graft-versus-host disease. N Engl J Med 367:135–145
47. Rossi R, Lichtner M, Sauzullo I, Mengoni F, Marocco R, Massetti AP, Mastroianni CM, Vullo V (2010) Downregulation of leukocyte migration after treatment with CCR5 antagonist maraviroc. J Acquir Immune Defic Syndr 54:e13–e14
48. Rossi R, Lichtner M, De Rosa A, Sauzullo I, Mengoni F, Massetti AP, Mastroianni CM, Vullo V (2011) In vitro effect of anti-human immunodeficiency virus CCR5 antagonist maraviroc on chemotactic activity of monocytes, macrophages and dendritic cells. Clin Exp Immunol 166:184–190
49. Rusconi S VP, Adorni F, et al. (2010). Maraviroc intensification for HIV-1-positive immunological non-responders despite virological suppression during HAART. In: Tenth International Congress on Drug Therapy in HIV Infection: Glasgow
50. Rusconi S, Vitiello P, Adorni F, Colella E, Foca E, Capetti A, Meraviglia P, Abeli C, Bonora S, D'Annunzio M, Di Biagio A, Di Pietro M, Butini L, Orofino G, Colafigli M, d'Ettorre G, Francisci D, Parruti G, Soria A, Buonomini AR, Tommasi C, Mosti S, Bai F, Di Nardo Stuppino S, Montano M, Tau P, Merlini E, Marchetti G (2013a) Maraviroc as intensification strategy in HIV-1 positive patients with deficient immunological response: an Italian randomized clinical trial. PLoS One 8:e80157
51. Schifitto G, Zhang J, Evans SR, Sacktor N, Simpson D, Millar LL, Hung VL, Miller EN, Smith E, Ellis RJ, Valcour V, Singer E, Marra CM, Kolson D, Weihe J, Remmel R, Katzenstein D, Clifford DB (2007) A multicenter trial of selegiline transdermal system for HIV-associated cognitive impairment. Neurology 69:1314–1321
52. Shikuma CM, Nakamoto B, Shiramizu B, Liang CY, DeGruttola V, Bennett K, Paul R, Kallianpur K, Chow D, Gavegnano C, Hurwitz SJ, Schinazi RF, Valcour VG (2012) Antiretroviral monocyte efficacy score linked to cognitive impairment in HIV. Antivir Ther 17:1233–1242
53. \Shikuma CM, Chow DC, Gangcuangco LM, Zhang G, Keating SM, Norris PJ, Seto TB, Parikh N, Kallianpur KJ, Nakamoto BK, Nagamine LS, Ndhlovu LC, Barbour JD (2014) Monocytes expand with immune dysregulation and is associated with insulin resistance in older individuals with chronic HIV. PLoS One 9:e90330
54. Shiramizu B, Ananworanich J, Chalermchai T, Siangphoe U, Troelstrup D, Shikuma C, De Grutolla V, Sithinamsuwan P, Praihirunkit P, Rattanamanee S, Valcour V, SEARCH 001.1 Study Group (2012) Failure to clear intra-monocyte HIV infection linked to persistent neuropsychological testing impairment after first-line combined antiretroviral therapy. J Neurovirol 18:69–73
55. Smurzynski M, Wu K, Letendre S, Robertson K, Bosch RJ, Clifford DB, Evans S, Collier AC, Taylor M, Ellis R (2011) Effects of central nervous system antiretroviral penetration on cognitive functioning in the ALLRT cohort. AIDS 25:357–365
56. Sonza S, Maerz A, Deacon N, Meanger J, Mills J, Crowe S (1996) Human immunodeficiency virus type 1 replication is blocked prior to reverse transcription and integration in freshly isolated peripheral blood monocytes. J Virol 70:3863–3869
57. S Rusconi, P Vitiello, F Adorni, E Colella, E Focà, A Capetti, P Meraviglia, C Abeli, S Bonora, M D’Annunzio, A Di Biagio, M Di Pietro, L Butini, G Orofino, M Colafigli, G d’Ettorre, D Francisci, G Parruti, A Soria, A R Buonomini, C Tommasi, S Mosti, F Bai, S Di Nardo Stuppino, M Morosi, M Montano, P Tau, E Merlini, G Marchetti (2013). Maraviroc as intensification strategy in HIV-1 positive patients with deficient immunological response: an Italian randomized clinical trial. PloS One. DOI: 10.1371/journal.pone.0080157
58. Tozzi V, Balestra P, Bellagamba R, Corpolongo A, Salvatori MF, Visco-Comandini U, Vlassi C, Giulianelli M, Galgani S, Antinori A, Narciso P (2007) Persistence of neuropsychologic deficits despite long-term highly active antiretroviral therapy in patients with HIV-related neurocognitive impairment: prevalence and risk factors. J Acquir Immune Defic Syndr 45:174–182
59. Tozzi V, Balestra P, Salvatori MF, Vlassi C, Liuzzi G, Giancola ML, Giulianelli M, Narciso P, Antinori A (2009) Changes in cognition during antiretroviral therapy: comparison of 2 different ranking systems to measure antiretroviral drug efficacy on HIV-associated neurocognitive disorders. J Acquir Immune Defic Syndr 52:56–63
60. Valcour VG, Shiramizu BT, Sithinamsuwan P, Nidhinandana S, Ratto-Kim S, Ananworanich J, Siangphoe U, Kim JH, de Souza M, Degruttola V, Paul RH, Shikuma CM, Southeast Asia Research Collaboration with the University of Hawaii 001 protocol team (2009) HIV DNA and cognition in a Thai longitudinal HAART initiation cohort: the SEARCH 001 cohort study. Neurology 72:992–998
61. Valcour VG, Ananworanich J, Agsalda M, Sailasuta N, Chalermchai T, Schuetz A, Shikuma C, Liang CY, Jirajariyavej S, Sithinamsuwan P, Tipsuk S, Clifford DB, Paul R, Fletcher JL, Marovich MA, Slike BM, DeGruttola V, Shiramizu B (2013) HIV DNA reservoir increases risk for cognitive disorders in cART-naive patients. PLoS One 8:e70164
62. Vera JH, Garvey LJ, Allsop JM, Kaye S, McClure MO, Back D, Taylor-Robinson SD, Winston A (2012) Alterations in cerebrospinal fluid chemokines are associated with maraviroc exposure and in vivo metabolites measurable by magnetic resonance spectroscopy. HIV Clin Trials 13:222–227
63. Westrop SJ, Moyle G, Jackson A, Nelson M, Mandalia S, Imami N (2012) CCR5 antagonism impacts vaccination response and immune profile in HIV-1 infection. Mol Med 18:1240–1248
64. Wilkin T LC, Tenorio A, et al. (2010). Maraviroc intensification for suboptimal CD4+ cell response despite sustained virologic suppression: ACTG 5256. In: 17th Conference on Retroviruses and Opportunistic Infections: San Francisco, CA
65. Yilmaz A, Price RW, Spudich S, Fuchs D, Hagberg L, Gisslen M (2008) Persistent intrathecal immune activation in HIV-1-infected individuals on antiretroviral therapy. J Acquir Immune Defic Syndr 47:168–173
66. Zawada AM, Rogacev KS, Rotter B, Winter P, Marell RR, Fliser D, Heine GH (2011) SuperSAGE evidence for CD14++CD16+ monocytes as a third monocyte subset. Blood 118:e50–e61
67. Zheng L, Taiwo B, Gandhi RT, Hunt PW, Collier AC, Flexner C, Bosch RJ (2014). Factors associated with CD8+ T-cell activation in HIV-1-infected patients on long-term antiretroviral therapy. J Acquir Immune Defic Syndr
68. Ziegler-Heitbrock HW (2000) Definition of human blood monocytes. J Leukoc Biol 67:603–606
69. Ziegler-Heitbrock L, Ancuta P, Crowe S, Dalod M, Grau V, Hart DN, Leenen PJ, Liu YJ, MacPherson G, Randolph GJ, Scherberich J, Schmitz J, Shortman K, Sozzani S, Strobl H, Zembala M, Austyn JM, Lutz MB (2010) Nomenclature of monocytes and dendritic cells in blood. Blood 116:e74–e80