The importance of monocytes and macrophages in HIV pathogenesis,treatment,and cure

AIDS

Volumn 28, Issue 15, 2014, Pages 2175-2187

  Campbell, Jennifer H ^a   Hearps, Anna C ^b,c   Martin, Genevieve E ^b   Williams, Kenneth C ^a   Crowe, Suzanne M ^b,c  

^a BOSTON COLLEGE   (United States)

^b ALFRED HOSPITAL   (Australia)

^c MONASH UNIVERSITY   (Australia)

Author keywords

HIV cure; HIV pathogenesis; Macrophage; Monocyte; Reservoirs

Indexed keywords

MARAVIROC; PHORBOL ESTER; RALTEGRAVIR; ROSUVASTATIN; VORINOSTAT;

ACQUIRED IMMUNE DEFICIENCY SYNDROME; ANTIVIRAL THERAPY; BONE MARROW CELL; BONE MARROW TRANSPLANTATION; CARDIOVASCULAR DISEASE; CARDIOVASCULAR RISK; CD4+ T LYMPHOCYTE; CELL ACTIVATION; CELL LINEAGE; HIV ASSOCIATED DEMENTIA; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; INFLAMMATION; MACROPHAGE; MACROPHAGE ACTIVATION; MONOCYTE; NEUROLOGIC DISEASE; NONHUMAN; OPPORTUNISTIC INFECTION; PERSISTENT INFECTION; PRIORITY JOURNAL; REVIEW; VIRAL CLEARANCE; VIRUS LOAD; VIRUS PATHOGENESIS; VIRUS REPLICATION; COMPLICATION; HIV INFECTIONS; IMMUNOLOGY; PATHOLOGY; TRANSMISSION; VIROLOGY;

AIDS DEMENTIA COMPLEX; CARDIOVASCULAR DISEASES; HIV INFECTIONS; HUMANS; MACROPHAGES; MONOCYTES;

EID: 84927734923     PISSN: 02699370     EISSN: 14735571     Source Type: Journal    
DOI: 10.1097/QAD.0000000000000408     Document Type: Review

References (170)

1. Crowe S, Mills J, McGrath MS. Quantitative immunocytofluorographic analysis of CD4 surface antigen expression and HIV infection of human peripheral blood monocyte/macrophages. AIDS Res Hum Retroviruses 1987; 3:135-145.
2. Gendelman HE, Orenstein JM, Martin MA, Ferrua C, Mitra R, Phipps T, et al. Efficient isolation and propagation of human immunodeficiency virus on recombinant colony-stimulating factor 1-treated monocytes. J Exp Med 1988; 167:1428-1441.
3. Zhu T, Muthui D, Holte S, Nickle D, Feng F, Brodie S, et al. Evidence for human immunodeficiency virus type 1 replication in vivo in CD14(R) monocytes and its potential role as a source of virus in patients on highly active antiretroviral therapy. J Virol 2002; 76:707-716.
4. Bacchus C, Cheret A, Avettand-Fenoël V, Nembot G, Mélard A, Blanc C, et al. A single HIV-1 cluster and a skewed immune homeostasis drive the early spread of HIV among resting CD4R cell subsets within one month postinfection. PLoS One 2013; 8:e64219.
5. Ziegler-Heitbrock L, Ancuta P, Crowe S, Dalod M, Grau V, Hart DN, et al. Nomenclature of monocytes and dendritic cells in blood. Blood 2010; 116:e74-e80.
6. Funderburg NT, Zidar DA, Shive C, Lioi A, Mudd J, Musselwhite LW, et al. Shared monocyte subset phenotypes in HIV-1 infection and in uninfected subjects with acute coronary syndrome. Blood 2012; 120:4599-4608.
7. Funderburg NT, Jiang Y, Debanne SM, Storer N, Labbato D, Clagett B, et al. Rosuvastatin treatment reduces markers of monocyte activation in HIV infected subjects on antiretroviral therapy. Clin Infect Dis 2013; 58:588-595.
8. Ziegler-Heitbrock L, Hofer TPJ. Toward a refined definition of monocyte subsets. Front Immunol 2013; 4:23.
9. Weber C, Belge KU, Hundelshausen von P, Draude G, Steppich B, Mack M, et al. Differential chemokine receptor expression and function in human monocyte subpopulations. J Leukoc Biol 2000; 67:699-704.
10. Thieblemont N, Weiss L, Sadeghi HM, Estcourt C, Haeffner-Cavaillon N. CD14lowCD16high: A cytokine-producing monocyte subset which expands during human immunodeficiency virus infection. Eur J Immunol 1995; 25:3418-3424.
11. Pulliam L, Gascon R, Stubblebine M, McGuire D, McGrath MS. Unique monocyte subset in patients with AIDS dementia. Lancet 1997; 349:692-695.
12. Han J, Wang B, Han N, Zhao Y, Song C, Feng X, et al. CD14(high)CD16(R) rather than CD14(low)CD16(R) monocytes correlate with disease progression in chronic HIV-infected patients. J Acquir Immune Defic Syndr 2009; 52:553- 559.
13. Barbour JD, Jalbert EC, Chow DC, Gangcuangco LM, Norris PJ, Keating SM, et al. 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. Atherosclerosi 2014; 232:52-58.
14. Jurriaans S, Dekker JT, de Ronde A. HIV-1 viral DNA load in peripheral blood mononuclear cells from seroconverters and long-term infected individuals. AIDS 1992; 6:635-641.
15. Bagasra O, Pomerantz RJ. Human immunodeficiency virus type I provirus is demonstrated in peripheral blood monocytes in vivo: A study utilizing an in situ polymerase chain reaction. AIDS Res Hum Retroviruses 1993; 9:69-76.
16. Bergamini A, Bolacchi F, Pesce CD, Carbone M, Cepparulo M, Demin F, et al. Increased CD4 and CCR5 expression and human immunodeficiency virus type 1 entry in CD40 ligand-stimulated macrophages. J Infect Dis 2002; 185:1567- 1577.
17. Sonza S, Maerz A, Deacon N, Meanger J, Mills J, Crowe S. Human immunodeficiency virus type 1 replication is blocked prior to reverse transcription and integration in freshly isolated peripheral blood monocytes. J Virol 1996; 70:3863- 3869.
18. Ellery PJ, Tippett E, Chiu Y-L, Paukovics G, Cameron PU, Solomon A, et al. The CD16R monocyte subset is more permissive to infection and preferentially harbors HIV-1 in vivo. J Immunol 2007; 178:6581-6589.
19. Jaworowski A, Kamwendo DD, Ellery P, Sonza S, Mwapasa V, Tadesse E, et al. CD16R monocyte subset preferentially harbors HIV-1 and is expanded in pregnant Malawian women with Plasmodium falciparum malaria and HIV-1 infection. J Infect Dis 2007; 196:38-42.
20. Berger A, Sommer AFR, Zwarg J, Hamdorf M, Welzel K, Esly N, et al. SAMHD1-deficient CD14R cells from individuals with Aicardi-Goutières syndrome are highly susceptible to HIV-1 infection. PLoS Pathog 2011; 7:e1002425.
21. Berger G, Durand S, Fargier G, Nguyen X-N, Cordeil S, Bouaziz S, et al. APOBEC3A is a specific inhibitor of the early phases of HIV-1 infection in myeloid cells. PLoS Pathog 2011; 7:e1002221.
22. Nasr N, Maddocks S, Turville SG, Harman AN, Woolger N, Helbig KJ, et al. HIV-1 infection of human macrophages directly induces viperin which inhibits viral production. Blood 2012; 120:778-788.
23. Nguyen LA, Kim D-H, Daly MB, Allan KC, Kim B. Host SAMHD1 protein promotes HIV-1 recombination in macrophages. J Biol Chem 2014; 289:2489-2496.
24. Peng G, Greenwell-Wild T, Nares S, Jin W, Lei KJ, Rangel ZG, et al. Myeloid differentiation and susceptibility to HIV-1 are linked to APOBEC3 expression. Blood 2007; 110:393-400.
25. Lahouassa H, Daddacha W, Hofmann H, Ayinde D, Logue EC, Dragin L, et al. SAMHD1 restricts the replication of human immunodeficiency virus type 1 by depleting the intracellular pool of deoxynucleoside triphosphates. Nat Immunol 2012; 13:223-228.
26. Laguette N, Sobhian B, Casartelli N, Ringeard M, Chable- Bessia C, Ségéral E, et al. SAMHD1 is the dendritic- And myeloid-cell-specific HIV-1 restriction factor counteracted by Vpx. Nature 2011; 474:654-657.
27. Wang X, Ye L, Hou W, Zhou Y, Wang Y-J, Metzger DS, et al. Cellular microRNA expression correlates with susceptibility of monocytes/macrophages to HIV-1 infection. Blood 2009; 113:671-674.
28. Williams KC, Burdo TH. HIV and SIV infection: The role of cellular restriction and immune responses in viral replication and pathogenesis. APMIS 2009; 117:400-412.
29. Kilareski EM, Shah S, Nonnemacher MR, Wigdahl B. Regulation of HIV-1 transcription in cells of the monocyte-macrophage lineage. Retrovirology 2009; 6:118.
30. He J, Chen Y, Farzan M, Choe H, Ohagen A, Gartner S, et al. CCR3 and CCR5 are co-receptors for HIV-1 infection of microglia. Nature 1997; 385:645-649.
31. Lavi E, Strizki JM, Ulrich AM, Zhang W, Fu L, Wang Q, et al. CXCR-4 (Fusin), a co-receptor for the type 1 human immunodeficiency virus (HIV-1), is expressed in the human brain in a variety of cell types, including microglia and neurons. Am J Pathol 1997; 151:1035-1042.
32. Williams KC, Corey S, Westmoreland SV, Pauley D, Knight H, deBakker C, et al. Perivascular macrophages are the primary cell type productively infected by simian immunodeficiency virus in the brains of macaques: implications for the neuropathogenesis of AIDS. J Exp Med 2001; 193:905-915.
33. Sinclair E, Gray F, Ciardi A, Scaravilli F. Immunohistochemical changes and PCR detection of HIV provirus DNA in brains of asymptomatic HIV-positive patients. J Neuropathol Exp Neurol 1994; 53:43-50.
34. Cai Y, Sugimoto C, Arainga M, Alvarez X, Didier ES, Kuroda MJ. In vivo characterization of alveolar and interstitial lung macrophages in rhesus macaques: implications for understanding lung disease in humans. J Immunol 2014; 192:2821-2829.
35. Jambo KC, Banda DH, Kankwatira AM, Sukumar N, Allain TJ, Heyderman RS, et al. Small alveolar macrophages are infected preferentially by HIV and exhibit impaired phagocytic function. Mucosal Immunol 2014; 7:1116-1126.
36. Zhang J, Zhu J, Imrich A, Cushion M, Kinane TB, Koziel H. Pneumocystis activates human alveolar macrophage NF-kappaB signaling through mannose receptors. Infect Immun 2004; 72:3147-3160.
37. Segal LN, Methé BA, Nolan A, Hoshino Y, Rom WN, Dawson R, et al. HIV-1 and bacterial pneumonia in the era of antiretroviral therapy. Proc Am Thorac Soc 2011; 8:282-287.
38. Allers K, Fehr M, Conrad K, Epple H-J, Schürmann D, Geelhaar-Karsch A, et al. Macrophages accumulate in the gut mucosa of untreated HIV-infected patients. J Infect Dis 2014; 209:739-748.
39. Shen R, Meng G, Ochsenbauer C, Clapham PR, Grams J, Novak L, et al. Stromal down-regulation of macrophage CD4/CCR5 expression and NF-B activation mediates HIV- 1 nonpermissiveness in intestinal macrophages. PLoS Pathog 2011; 7:e1002060.
40. Zaritsky LA, Dery A, Leong WY, Gama L, Clements JE. Tissuespecific interferon alpha subtype response to SIV infection in brain, spleen, and lung. J Interferon Cytokine Res 2013; 33:24- 33.
41. Hirsch VM, Lifson JD. Simian immunodeficiency virus infection of monkeys as a model system for the study of AIDS pathogenesis, treatment, and prevention. Adv Pharmacol 2000; 49:437-477.
42. Williams K, Burdo TH. Monocyte mobilization, activation markers, and unique macrophage populations in the brain: observations from SIV infected monkeys are informative with regard to pathogenic mechanisms of HIV infection in humans. J Neuroimmune Pharmacol 2012; 7:363-371.
43. Whitelaw DM. Observations on human monocyte kinetics after pulse labeling. Cell Tissue Kinet 1972; 5:311-317.
44. Hasegawa A, Liu H, Ling B, Borda JT, Alvarez X, Sugimoto C, et al. The level of monocyte turnover predicts disease progression in the macaque model of AIDS. Blood 2009; 114:2917- 2925.
45. Hearps AC, Maisa A, Cheng W-J, Angelovich TA, Lichtfuss GF, Palmer CS, et al. HIV infection induces age-related changes to monocytes and innate immune activation in young males which persist despite cART. AIDS 2012; 26:843-853.
46. Clements JE, Babas T, Mankowski JL, Suryanarayana K, Piatak M, Tarwater PM, et al. The central nervous system as a reservoir for simian immunodeficiency virus (SIV): Steadystate levels of SIV DNA in brain from acute through asymptomatic infection. J Infect Dis 2002; 186:905-913.
47. Igarashi T, Imamichi H, Brown CR, Hirsch VM, Martin MA. The emergence and characterization of macrophage-tropic SIV/HIV chimeric viruses (SHIVs) present in CD4R T celldepleted rhesus monkeys. J Leukoc Biol 2003; 74:772-780.
48. Heath L, Fox A, McClure J, Diem K, van't Wout AB, Zhao H, et al. Evidence for limited genetic compartmentalization of HIV-1 between lung and blood. PLoS One 2009; 4:e6949.
49. Cheng-Mayer C, Weiss C, Seto D, Levy JA. Isolates of human immunodeficiency virus type 1 from the brain may constitute a special group of the AIDS virus. Proc Natl Acad Sci U S A 1989; 86:8575-8579.
50. Wong JK, Ignacio CC, Torriani F, Havlir D, Fitch NJ, Richman DD. In vivo compartmentalization of human immunodeficiency virus: evidence from the examination of pol sequences from autopsy tissues. J Virol 1997; 71:2059-2071.
51. Chen H, Wood C, Petito CK. Comparisons of HIV-1 viral sequences in brain, choroid plexus and spleen: Potential role of choroid plexus in the pathogenesis of HIV encephalitis. J Neurovirol 2000; 6:498-506.
52. Stingele K, Haas J, Zimmermann T, Stingele R, Hübsch-Müller C, Freitag M, et al. Independent HIV replication in paired CSF and blood viral isolates during antiretroviral therapy. Neurology 2001; 56:355-361.
53. Ghorpade A, Nukuna A, Che M, Haggerty S, Persidsky Y, Carter E, et al. Human immunodeficiency virus neurotropism: An analysis of viral replication and cytopathicity for divergent strains in monocytes and microglia. J Virol 1998; 72:3340- 3350.
54. Gorry PR, Bristol G, Zack JA, Ritola K, Swanstrom R, Birch CJ, et al. Macrophage tropism of human immunodeficiency virus type 1 isolates from brain and lymphoid tissues predicts neurotropism independent of coreceptor specificity. J Virol 2001; 75:10073-10089.
55. Peters PJ, Bhattacharya J, Hibbitts S, Dittmar MT, Simmons G, Bell J, et al. Biological analysis of human immunodeficiency virus type 1 R5 envelopes amplified from brain and lymph node tissues of AIDS patients with neuropathology reveals two distinct tropism phenotypes and identifies envelopes in the brain that confer an enhanced tropism and fusigenicity for macrophages. J Virol 2004; 78:6915-6926.
56. Salemi M, Lamers SL, Yu S, de Oliveira T, Fitch WM, McGrath MS. Phylodynamic analysis of human immunodeficiency virus type 1 in distinct brain compartments provides a model for the neuropathogenesis of AIDS. J Virol 2005; 79:11343-11352.
57. Strickland SL, Gray RR, Lamers S, Burdo T, Huenink E, Nolan D, et al. Efficient transmission and persistence of low frequency SIVmac251 variants in CD8-depleted rhesus macaques with different neuropathology. J Gen Virol 2012; 93:925-938.
58. Martin GE, Gouillou M, Hearps AC, Angelovich TA, Cheng AC, Lynch F, et al. Age-associated changes in monocyte and innate immune activation markers occur more rapidly in HIV infected women. PLoS One 2013; 8:e55279.
59. Krishnan S, Wilson EMP, Sheikh V, Rupert A, Mendoza D, Yang J, et al. Evidence for innate immune system activation in HIV type 1-infected elite controllers. J Infect Dis 2014; 209: 931-939.
60. Mavigner M, Delobel P, Cazabat M, Dubois M, L'faqihi-Olive F-E, Raymond S, et al. HIV-1 residual viremia correlates with persistent T-cell activation in poor immunological responders to combination antiretroviral therapy. PLoS One 2009; 4:e7658.
61. Kedzierska K, Ellery P, Mak J, Lewin SR, Crowe SM, Jaworowski A. HIV-1 down-modulates gamma signaling chain of Fc gamma R in human macrophages: A possible mechanism for inhibition of phagocytosis. J Immunol 2002; 168:2895-2903.
62. Leeansyah E, Wines BD, Crowe SM, Jaworowski A. The mechanism underlying defective Fcgamma receptor-mediated phagocytosis by HIV-1-infected human monocyte-derived macrophages. J Immunol 2007; 178:1096-1104.
63. Périssé ARS, Smeaton L, Chen Y, La Rosa A, Walawander A, Nair A, et al. Outcomes among HIV-1 infected individuals first starting antiretroviral therapy with concurrent active TB or other AIDS-defining disease. PLoS One 2013; 8:e83643.
64. Meintjes G, Lawn SD, Scano F, Maartens G, French MA, Worodria W, et al. Tuberculosis-associated immune reconstitution inflammatory syndrome: case definitions for use in resource-limited settings. Lancet Infect Dis 2008; 8:516-523.
65. Tran HTT, Van den Bergh R, Loembé MM, Worodria W, Mayanja-Kizza H, Colebunders R, et al. Modulation of the complement system in monocytes contributes to tuberculosisassociated immune reconstitution inflammatory syndrome. AIDS 2013; 27:1725-1734.
66. Tran HTT, Van den Bergh R, Vu TN, Laukens K, Worodria W, Loembé MM, et al. The role of monocytes in the development of tuberculosis-associated immune reconstitution inflammatory syndrome. Immunobiology 2014; 219:37-44.
67. Heaton RK, Clifford DB, Franklin DR, Woods SP, Ake C, Vaida F, et al. HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy: CHARTER Study. Neurology 2010; 75:2087-2096.
68. Heaton RK, Franklin DR, Ellis RJ, McCutchan JA, Letendre SL, Leblanc S, et al. HIV-associated neurocognitive disorders before and during the era of combination antiretroviral therapy: differences in rates, nature, and predictors. J Neurovirol 2011; 17:3-16.
69. Vivithanaporn P, Heo G, Gamble J, Krentz HB, Hoke A, Gill MJ, et al. Neurologic disease burden in treated HIV/AIDS predicts survival: A population-based study. Neurology 2010; 75:1150-1158.
70. Tozzi V, Balestra P, Serraino D, Bellagamba R, Corpolongo A, Piselli P, et al. Neurocognitive impairment and survival in a cohort of HIV-infected patients treated with HAART. AIDS Res Hum Retroviruses 2005; 21:706-713.
71. Cosenza MA, Zhao M-L, Si Q, Lee SC. Human brain parenchymal microglia express CD14 and CD45 and are productively infected by HIV-1 in HIV-1 encephalitis. Brain Pathol 2002; 12:442-455.
72. Gelman BB, Lisinicchia JG, Morgello S, Masliah E, Commins D, Achim CL, et al. Neurovirological correlation with HIV-associated neurocognitive disorders and encephalitis in a HAARTera cohort. J Acquir Immune Defic Syndr 2013; 62:487-495.
73. Williams K, Westmoreland S, Greco J, Ratai E, Lentz M, Kim W-K, et al. Magnetic resonance spectroscopy reveals that activated monocytes contribute to neuronal injury in SIV neuroAIDS. J Clin Invest 2005; 115:2534-2545.
74. Campbell JH, Burdo TH, Autissier P, Bombardier JP, Westmoreland SV, Soulas C, et al. Minocycline inhibition of monocyte activation correlates with neuronal protection in SIV neuroAIDS. PLoS One 2011; 6:e18688.
75. Kusao I, Shiramizu B, Liang C-Y, Grove J, Agsalda M, Troelstrup D, et al. Cognitive performance related to HIV- 1-infected monocytes. J Neuropsychiatry Clin Neurosci 2012; 24:71-80.
76. Fischer-Smith T, Croul S, Sverstiuk AE, Capini C, L'Heureux D, Régulier EG, et al. CNS invasion by CD14R/CD16R peripheral blood-derived monocytes in HIV dementia: Perivascular accumulation and reservoir of HIV infection. J Neurovirol 2001; 7:528-541.
77. Kamat A, Lyons JL, Misra V, Uno H, Morgello S, Singer EJ, et al. Monocyte activation markers in cerebrospinal fluid associated with impaired neurocognitive testing in advanced HIV infection. J Acquir Immune Defic Syndr 2012; 60:234-243.
78. Lyons JL, Uno H, Ancuta P, Kamat A, Moore DJ, Singer EJ, 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; 57:371-379.
79. Ancuta P, Kamat A, Kunstman KJ, Kim E-Y, Autissier P, Wurcel A, et al. Microbial translocation is associated with increased monocyte activation and dementia in AIDS patients. PLoS One 2008; 3:e2516.
80. Kim W-K, Corey S, Alvarez X, Williams K. Monocyte/macrophage traffic in HIV and SIV encephalitis. J Leukoc Biol 2003; 74:650-656.
81. Williams DW, Eugenin EA, Calderon TM, Berman JW. Monocyte maturation, HIV susceptibility, and transmigration across the blood brain barrier are critical in HIV neuropathogenesis. J Leukoc Biol 2012; 91:401-415.
82. Kamat A, Misra V, Cassol E, Ancuta P, Yan Z, Li C, et al. A plasma biomarker signature of immune activation in HIV patients on antiretroviral therapy. PLoS One 2012; 7:e30881.
83. Shikuma CM, Nakamoto B, Shiramizu B, Liang C-Y, Degruttola V, Bennett K, et al. Antiretroviral monocyte efficacy score linked to cognitive impairment in HIV. Antivir Ther (Lond) 2012; 17:1233-1242.
84. Wang H, Sun J, Goldstein H. Human immunodeficiency virus type 1 infection increases the in vivo capacity of peripheral monocytes to cross the blood-brain barrier into the brain and the in vivo sensitivity of the blood-brain barrier to disruption by lipopolysaccharide. J Virol 2008; 82:7591-7600.
85. Williams K, Alvarez X, Lackner AA. Central nervous system perivascular cells are immunoregulatory cells that connect the CNS with the peripheral immune system. Glia 2001; 36:156- 164.
86. Kim W-K, Alvarez X, Fisher J, Bronfin B, Westmoreland S, McLaurin J, et al. CD163 identifies perivascular macrophages in normal and viral encephalitic brains and potential precursors to perivascular macrophages in blood. Am J Pathol 2006; 168:822-834.
87. Xiong H, Zeng YC, Lewis T, Zheng J, Persidsky Y, Gendelman HE. HIV-1 infected mononuclear phagocyte secretory products affect neuronal physiology leading to cellular demise: relevance for HIV-1-associated dementia. J Neurovirol 2000; 6 (Suppl 1):S14-23.
88. Persidsky Y, Zheng J, Miller D, Gendelman HE. Mononuclear phagocytes mediate blood-brain barrier compromise and neuronal injury during HIV-1-associated dementia. J Leukoc Biol 2000; 68:413-422.
89. Nottet HS, Persidsky Y, Sasseville VG, Nukuna AN, Bock P, Zhai QH, et al. Mechanisms for the transendothelial migration of HIV-1-infected monocytes into brain. J Immunol 1996; 156:1284-1295.
90. Persidsky Y, Stins M, Way D, Witte MH, Weinand M, Kim KS, et al. A model for monocyte migration through the bloodbrain barrier during HIV-1 encephalitis. J Immunol 1997; 158:3499-3510.
91. Williams DW, Calderon TM, Lopez L, Carvallo-Torres L, Gaskill PJ, Eugenin EA, et al. Mechanisms of HIV entry into the CNS: increased sensitivity of HIV infected CD14RCD16R monocytes to CCL2 and key roles of CCR2, JAM-A, and ALCAM in diapedesis. PLoS One 2013; 8:e69270.
92. Davis LE, Hjelle BL, Miller VE, Palmer DL, Llewellyn AL, Merlin TL, et al. Early viral brain invasion in iatrogenic human immunodeficiency virus infection. Neurology 1992; 42:1736-1739.
93. Chakrabarti L, Hurtrel M, Maire MA, Vazeux R, Dormont D, Montagnier L, et al. Early viral replication in the brain of SIVinfected rhesus monkeys. Am J Pathol 1991; 139:1273-1280.
94. Clay CC, Rodrigues DS, Ho YS, Fallert BA, Janatpour K, Reinhart TA, et al. Neuroinvasion of fluorescein-positive monocytes in acute simian immunodeficiency virus infection. J Virol 2007; 81:12040-12048.
95. Soulas C, Conerly C, Kim W-K, Burdo TH, Alvarez X, Lackner AA, et al. Recently infiltrating MAC387(R) monocytes/macrophages a third macrophage population involved in SIV and HIV encephalitic lesion formation. Am J Pathol 2011; 178:2121-2135.
96. 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; 27:1387-1395.
97. Burdo TH, Soulas C, Orzechowski K, Button J, Krishnan A, Sugimoto C, et al. Increased monocyte turnover from bone marrow correlates with severity of SIV encephalitis and CD163 levels in plasma. PLoS Pathog 2010; 6:e1000842.
98. Valcour VG, Shiramizu BT, Shikuma CM. HIV DNA in circulating monocytes as a mechanism to dementia and other HIV complications. J Leukoc Biol 2010; 87:621-626.
99. Valcour VG. HIV, aging, and cognition: emerging issues. Top Antivir Med 2013; 21:119-123.
100. Hearps AC, Martin GE, Rajasuriar R, Crowe SM. Inflammatory Co-morbidities in HIVR Individuals: Learning Lessons from Healthy Ageing. Curr HIV/AIDS Rep 2014; 11:20-34.
101. Hsu DC, Sereti I, Ananworanich J. Serious Non-AIDS events: Immunopathogenesis and interventional strategies. AIDS Res Ther 2013; 10:29.
102. Tenorio AR, Zheng Y, Bosch RJ, Krishnan S, Rodriguez B, Hunt PW, et al. Soluble markers of inflammation and coagulation, but not T-cell activation, are predictors of non-AIDS-defining morbid events during suppressive antiretroviral treatment. J Infect Dis 2014 (in press).
103. Kuller LH, Tracy R, Belloso W, De Wit S, Drummond F, Lane HC, et al. Inflammatory and coagulation biomarkers and mortality in patients with HIV infection. PLoS Med 2008; 5:e203.
104. Sandler NG, Wand H, Roque A, Law M, Nason MC, Nixon DE, et al. Plasma levels of soluble CD14 independently predict mortality in HIV infection. J Infect Dis 2011; 203:780-790.
105. Bukh AR, Melchjorsen J, Offersen R, Jensen JMB, Toft L, Støvring H, et al. Endotoxemia is associated with altered innate and adaptive immune responses in untreated HIV-1 infected individuals. PLoS One 2011; 6:e21275.
106. Hoy J. Bone, fracture and frailty. Curr Opin HIV AIDS 2011; 6:309-314.
107. Brown TT, Qaqish RB. Antiretroviral therapy and the prevalence of osteopenia and osteoporosis: A meta-analytic review. AIDS 2006; 20:2165-2174.
108. Gazzola L, Bellistri GM, Tincati C, Ierardi V, Savoldi A, del Dole A, et al. Association between peripheral T-Lymphocyte activation and impaired bone mineral density in HIV-infected patients. J Transl Med 2013; 11:51.
109. Erlandson KM, O'Riordan M, Labbato D, McComsey GA. Relationships between inflammation, immune activation, and bone health among HIV-infected adults on stable antiretroviral therapy. J Acquir Immune Defic Syndr 2014; 65:290-298.
110. Desquilbet L, Jacobson LP, Fried LP, Phair JP, Jamieson BD, Holloway M, et al. HIV-1 infection is associated with an earlier occurrence of a phenotype related to frailty. J Gerontol A Biol Sci Med Sci 2007; 62:1279-1286.
111. Qu T, Yang H, Walston JD, Fedarko NS, Leng SX. Upregulated monocytic expression of CXC chemokine ligand 10 (CXCL-10) and its relationship with serum interleukin-6 levels in the syndrome of frailty. Cytokine 2009; 46:319-324.
112. Hemkens LG, Bucher HC. HIV infection and cardiovascular disease. Eur Heart J 2014; 35:1373-1381.
113. Parra S, Coll B, Aragonés G, Marsillach J, Beltrán R, Rull A, et al. Nonconcordance between subclinical atherosclerosis and the calculated Framingham risk score in HIV-infected patients: relationships with serum markers of oxidation and inflammation. HIV Med 2010; 11:225-231.
114. Moore KJ, Sheedy FJ, Fisher EA. Macrophages in atherosclerosis: A dynamic balance. Nat Rev Immunol 2013; 13: 709-721.
115. Baker JV, Hullsiek KH, Singh A, Wilson E, Henry K, Lichtenstein K, et al. Immunologic predictors of coronary artery calcium progression in a contemporary HIV cohort. AIDS 2013; 28:831-840.
116. Duprez DA, Neuhaus J, Kuller LH, Tracy R, Belloso W, De Wit S, et al. Inflammation, coagulation and cardiovascular disease in HIV-infected individuals. PLoS ONE 2012; 7:e44454.
117. De Luca A, de Gaetano Donati K, Colafigli M, Cozzi-Lepri A, De Curtis A, Gori A, et al. The association of high-sensitivity c-reactive protein and other biomarkers with cardiovascular disease in patients treated for HIV: A nested case-control study. BMC Infect Dis 2013; 13:414.
118. Shikuma CM, Barbour JD, Ndhlovu LC, Keating SM, Norris PJ, Budoff M, et al. Plasma monocyte chemoattractant protein-1 and tumor necrosis factor-( levels predict the presence of coronary artery calcium in HIV-infected individuals independent of traditional cardiovascular risk factors. AIDS Res Hum Retroviruses 2014; 30:142-146.
119. Hsue PY, Scherzer R, Hunt PW, Schnell A, Bolger AF, Kalapus SC, et al. Carotid intima-media thickness progression in HIVinfected adults occurs preferentially at the carotid bifurcation and is predicted by inflammation. J Am Heart Assoc 2012; 1:e000422.
120. Westhorpe CLV, Maisa A, Spelman T, Hoy JF, Dewar EM, Karapanagiotidis S, et al. Associations between surface markers on blood monocytes and carotid atherosclerosis in HIV-positive individuals. Immunol Cell Biol 2014; 92:133- 138.
121. Llodrá J, Angeli V, Liu J, Trogan E, Fisher EA, Randolph GJ. Emigration of monocyte-derived cells from atherosclerotic lesions characterizes regressive, but not progressive, plaques. Proc Natl Acad Sci U S A 2004; 101:11779-11784.
122. Ghattas A, Griffiths HR, Devitt A, Lip GYH, Shantsila E. Monocytes in coronary artery disease and atherosclerosis: Where are we now? J Am Coll Cardiol 2013; 62:1541-1551.
123. Burdo TH, Lo J, Abbara S, Wei J, DeLelys ME, Preffer F, et al. Soluble CD163, a novel marker of activated macrophages, is elevated and associated with noncalcified coronary plaque in HIV-infected patients. J Infect Dis 2011; 204:1227-1236.
124. Fitch KV, Srinivasa S, Abbara S, Burdo TH, Williams KC, Eneh P, et al. Noncalcified coronary atherosclerotic plaque and immune activation in HIV-infected women. J Infect Dis 2013; 208:1737-1746.
125. Subramanian S, Tawakol A, Burdo TH, Abbara S, Wei J, Vijayakumar J, et al. Arterial inflammation in patients with HIV. JAMA 2012; 308:379-386.
126. Merlini E, Luzi K, Suardi E, Barassi A, Cerrone M, Martínez JS, et al. T-cell phenotypes, apoptosis and inflammation in HIVR patients on virologically effective cART with early atherosclerosis. PLoS One 2012; 7:e46073.
127. Kelesidis T, Kendall MA, Yang OO, Hodis HN, Currier JS. Biomarkers of microbial translocation and macrophage activation: Association with progression of subclinical atherosclerosis in HIV-1 infection. J Infect Dis 2012; 206:1558- 1567.
128. Longenecker CT, Funderburg NT, Jiang Y, Debanne S, Storer N, Labbato DE, et al. Markers of inflammation and CD8 T-cell activation, but not monocyte activation, are associated with subclinical carotid artery disease in HIV-infected individuals. HIV Med 2013; 14:385-390.
129. Longenecker CT, Jiang Y, Orringer CE, Gilkeson RC, Debanne S, Funderburg NT, et al. Soluble CD14 is independently associated with coronary calcification and extent of subclinical vascular disease in treated HIV infection. AIDS 2014; 28:969-977.
130. Barbour JD, Jalbert EC, Chow DC, Gangcuangco LMA, Norris PJ, Keating SM, et al. 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 antiretroviral therapy. Atherosclerosis 2014; 232: 52-58.
131. DAD study group. Friis-Møller N, Reiss P, Sabin CA, Weber R, Monforte AD, et al. Class of antiretroviral drugs and the risk of myocardial infarction. N Engl J Med 2007; 356:1723-1735.
132. Pereyra F, Lo J, Triant VA, Wei J, Buzon MJ, Fitch KV, et al. Increased coronary atherosclerosis and immune activation in HIV-1 elite controllers. AIDS 2012; 26:2409-2412.
133. Walker JA, Sulciner ML, Nowicki KD, Miller AD, Burdo TH, Williams KC. Elevated numbers of CD163(R) macrophages in hearts of simian immunodeficiency virus-infected monkeys correlate with cardiac pathology and fibrosis. AIDS Res Hum Retroviruses 2014; 30:685-694.
134. Westhorpe CLV, Zhou J, Webster NL, Kalionis B, Lewin SR, Jaworowski A, et al. Effects of HIV-1 infection in vitro on transendothelial migration by monocytes and monocytederived macrophages. J Leukoc Biol 2009; 85:1027-1035.
135. Maisa A, Pereira CF, Angelovich TA, Zhou JL, Muller WA, Hearps AC, et al. TNF drives foam cell formation by monocytes from HIVR donors in an in vitro atherosclerosis model. [Abstract 256]. 21st Conference on Retroviruses and Opportunistic Infections, Boston MA, March 2014.
136. Hütter G, Nowak D, Mossner M, Ganepola S, Müssig A, Allers K, et al. Long-term control of HIV by CCR5Delta32/Delta32 stem-cell transplantation. N Engl J Med 2009; 360:692-698.
137. Henrich TJ, Gandhi RT. Early treatment and HIV-1 reservoirs: A stitch in time? J Infect Dis 2013; 208:1189-1193.
138. Henrich T, Hill AL, Goldstein E, Rosenbloom DIS, Hanhauser E, Kuritzkes DR. Mathematical modeling of HIV-1 latent reservoir dynamics following hematopoietic stem cell transplantation. [Abstract 130]. 6th International Workshop on HIV Persistence, Miami FL, December 2013.
139. Migueles SA, Connors M. Long-term nonprogressive disease among untreated HIV-infected individuals: clinical implications of understanding immune control of HIV. JAMA 2010; 304:194-201.
140. Blankson JN, Bailey JR, Thayil S, Yang H-C, Lassen K, Lai J, et al. Isolation and characterization of replication-competent human immunodeficiency virus type 1 from a subset of elite suppressors. J Virol 2007; 81:2508-2518.
141. Spivak AM, Salgado M, Rabi SA, O'Connell KA, Blankson JN. Circulating monocytes are not a major reservoir of HIV-1 in elite suppressors. J Virol 2011; 85:10399-10403.
142. Sonza S, Mutimer HP, Oelrichs R, Jardine D, Harvey K, Dunne A, et al. Monocytes harbour replication-competent, nonlatent HIV-1 in patients on highly active antiretroviral therapy. AIDS 2001; 15:17-22.
143. Lambotte O, Taoufik Y, de Goër MG, Wallon C, Goujard C, Delfraissy JF. Detection of infectious HIV in circulating monocytes from patients on prolonged highly active antiretroviral therapy. J Acquir Immune Defic Syndr 2000; 23:114-119.
144. Ho Y-C, Shan L, Hosmane NN, Wang J, Laskey SB, Rosenbloom DIS, et al. Replication-competent noninduced proviruses in the latent reservoir increase barrier to HIV-1 cure. Cell 2013; 155:540-551.
145. Sahu GK, Paar D, Frost SDW, Smith MM, Weaver S, Cloyd MW. Low-level plasma HIVs in patients on prolonged suppressive highly active antiretroviral therapy are produced mostly by cells other than CD4 T-cells. J Med Virol 2009; 81:9-15.
146. Duncan CJA, Russell RA, Sattentau QJ. High multiplicity HIV- 1 cell-to-cell transmission from macrophages to CD4RT cells limits antiretroviral efficacy. AIDS 2013; 27:2201-2206.
147. Peressin M, Proust A, Schmidt S, Su B, Lambotin M, Biedma ME, et al. Efficient transfer of HIV-1 in trans and in cis from Langerhans dendritic cells and macrophages to autologous T lymphocytes. AIDS 2014; 28:667-677.
148. Gutiérrez C, Hernández-Novoa B, Vallejo A, Serrano-Villar S, Abad-Fernández M, Madrid N, et al. Dynamics of the HIV-1 latent reservoir after discontinuation of the intensification of antiretroviral treatment: results of two clinical trials. AIDS 2013; 27:2081-2088.
149. Josefsson L, Stockenstromvon S, Faria NR, Sinclair E, Bacchetti P, Killian M, et al. The HIV-1 reservoir in eight patients on long-term suppressive antiretroviral therapy is stable with few genetic changes over time. Proc Natl Acad Sci U S A 2013; 110:E4987-E4996.
150. Strain MC, Little SJ, Daar ES, Haavlir DV, Gunthard HF, Lam RY, et al. Effect of treatment, during primary infection, on establishment and clearance of cellular reservoirs of HIV-1. J Infect Dis 2005; 191:1410-1418.
151. Buzon MJ, Codoñer FM, Frost SDW, Pou C, Puertas MC, Massanella M, et al. Deep molecular characterization of HIV-1 dynamics under suppressive HAART. PLoS Pathog 2011; 7:e1002314.
152. Crowe SM, McGrath MS, Elbeik T, Kirihara J, Mills J. Comparative assessment of antiretrovirals in human monocytemacrophages and lymphoid cell lines acutely and chronically infected with the human immunodeficiency virus. J Med Virol 1989; 29:176-180.
153. Solas C, Lafeuillade A, Halfon P, Chadapaud S, Hittinger G, Lacarelle B. Discrepancies between protease inhibitor concentrations and viral load in reservoirs and sanctuary sites in human immunodeficiency virus-infected patients. Antimicrob Agents Chemother 2003; 47:238-243.
154. Aquaro S, Svicher V, Schols D, Pollicita M, Antinori A, Balzarini J, et al. Mechanisms underlying activity of antiretroviral drugs in HIV-1-infected macrophages: new therapeutic strategies. J Leukoc Biol 2006; 80:1103-1110.
155. Perno CF, Newcomb FM, Davis DA, Aquaro S, Humphrey RW, Caliò R, et al. Relative potency of protease inhibitors in monocytes/macrophages acutely and chronically infected with human immunodeficiency virus. J Infect Dis 1998; 178:413-422.
156. Brown KC, Patterson KB, Malone SA, Shaheen NJ, Prince HMA, Dumond JB, et al. Single and multiple dose pharmacokinetics of maraviroc in saliva, semen, and rectal tissue of healthy HIV-negative men. J Infect Dis 2011; 203:1484- 1490.
157. Scopelliti F, Pollicita M, Ceccherini-Silberstein F, Di Santo F, Surdo M, Aquaro S, et al. Comparative antiviral activity of integrase inhibitors in human monocyte-derived macrophages and lymphocytes. Antiviral Res 2011; 92:255- 261.
158. Yilmaz A, Gisslén M, Spudich S, Lee E, Jayewardene A, Aweeka F, et al. Raltegravir cerebrospinal fluid concentrations in HIV-1 infection. PLoS ONE 2009; 4:e6877.
159. Marsden MD, Avancena P, Kitchen CMR, Hubbard T, Zack JA. Single mutations in HIV integrase confer high-level resistance to raltegravir in primary human macrophages. Antimicrob Agents Chemother 2011; 55:3696-3702.
160. Cysique LA, Waters EK, Brew BJ. Central nervous system antiretroviral efficacy in HIV infection: A qualitative and quantitative review and implications for future research. BMC Neurol 2011; 11:148.
161. del Palacio M, Alvarez S, Muñoz-Fernández MÁ . HIV-1 infection and neurocognitive impairment in the current era. Rev Med Virol 2012; 22:33-45.
162. Schweinsburg BC, Taylor MJ, Alhassoon OM, Gonzalez R, Brown GG, Ellis RJ, et al. Brain mitochondrial injury in human immunodeficiency virus-seropositive (HIVR) individuals taking nucleoside reverse transcriptase inhibitors. J Neurovirol 2005; 11:356-364.
163. Robertson K, Liner J, Meeker RB. Antiretroviral neurotoxicity. J Neurovirol 2012; 18:388-399.
164. Edén A, Price RW, Spudich S, Fuchs D, Hagberg L, Gisslén M. Immune activation of the central nervous system is still present after >4 years of effective highly active antiretroviral therapy. J Infect Dis 2007; 196:1779-1783.
165. Kumar AM, Borodowsky I, Fernandez B, Gonzalez L, Kumar M. Human immunodeficiency virus type 1 RNA Levels in different regions of human brain: quantification using real-time reverse transcriptase-polymerase chain reaction. J Neurovirol 2007; 13:210-224.
166. Lamers SL, Gray RR, Salemi M, Huysentruyt LC, McGrath MS. HIV-1 phylogenetic analysis shows HIV-1 transits through the meninges to brain and peripheral tissues. Infect Genet Evol 2011; 11:31-37.
167. Katlama C, Deeks SG, Autran B, Martinez-Picado J, van Lunzen J, Rouzioux C, et al. Barriers to a cure for HIV: new ways to target and eradicate HIV-1 reservoirs. Lancet 2013; 381:2109-2117.
168. Kulkosky J, Culnan DM, Roman J, Dornadula G, Schnell M, Boyd MR, et al. Prostratin: Activation of latent HIV-1 expression suggests a potential inductive adjuvant therapy for HAART. Blood 2001; 98:3006-3015.
169. Archin NM, Espeseth A, Parker D, Cheema M, Hazuda D, Margolis DM. Expression of latent HIV induced by the potent HDAC inhibitor suberoylanilide hydroxamic acid. AIDS Res Hum Retroviruses 2009; 25:207-212.
170. Archin NM, Liberty AL, Kashuba AD, Choudhary SK, Kuruc JD, Crooks AM, et al. Administration of vorinostat disrupts HIV-1 latency in patients on antiretroviral therapy. Nature 2012; 487:482-485.