HIV-1-associated dementia during HAART therapy

Recent Patents on CNS Drug Discovery

Volumn 3, Issue 1, 2008, Pages 23-33

  Aquaro, Stefano ^a,b   Svicher, Valentina ^a   Ronga, Luigi ^a   Perno, Carlo F ^a   Pollicita, Michela ^a  

^a UNIVERSITY OF ROME TOR VERGATA   (Italy)

^b UNIVERSITY OF CALABRIA   (Italy)

Author keywords

Anti HIV drugs; Central nervous system; NeuroAIDS

Indexed keywords

8 [4 (2 BUTOXYETHOXY)PHENYL] 1,2,3,4 TETRAHYDRO 1 ISOBUTYL N [4 (1 PROPYL 1H IMIDAZOL 5 YLMETHYLSULFINYL)PHENYL] 1 BENZAZOCINE 5 CARBOXAMIDE; ANTIOXIDANT; ANTIRETROVIRUS AGENT; BEVIRIMAT; CHEMOKINE RECEPTOR CCR5 ANTAGONIST; CPI 1189; EFAVIRENZ; ELVITEGRAVIR; ENDOTHELIAL LEUKOCYTE ADHESION MOLECULE 1; ENFUVIRTIDE; INTEGRASE INHIBITOR; INTERCELLULAR ADHESION MOLECULE 1; INTERLEUKIN 8; MANGANESE TETRAKIS(4 BENZOIC ACID)PORPHYRIN CHLORIDE; MARAVIROC; N [4 [[[6,7 DIHYDRO 2 (4 METHYLPHENYL) 5H BENZOCYCLOHEPTEN 8 YL]CARBONYL]AMINO]BENZYL] N,N DIMETHYL 2H TETRAHYDROPYRAN 4 AMINIUM CHLORIDE; NEVIRAPINE; PEPTIDE T; PLANT LECTIN; PRO 140; PROTEINASE INHIBITOR; RALTEGRAVIR; RNA DIRECTED DNA POLYMERASE INHIBITOR; SELEGILINE; SELENIUM; SHIKONIN; T 1249; UNCLASSIFIED DRUG; UNINDEXED DRUG; VASCULAR CELL ADHESION MOLECULE 1; VICRIVIROC;

ACQUIRED IMMUNE DEFICIENCY SYNDROME; ANTIVIRAL ACTIVITY; ASTROCYTE; BLOOD BRAIN BARRIER; BRAIN NERVE CELL; BRAIN PROTECTION; CLINICAL TRIAL; COGNITIVE DEFECT; DEMENTIA; DOSE RESPONSE; DRUG BIOAVAILABILITY; DRUG BRAIN LEVEL; DRUG CEREBROSPINAL FLUID LEVEL; DRUG DESIGN; DRUG EFFICACY; DRUG PENETRATION; DRUG POTENCY; DRUG SELECTIVITY; DRUG TARGETING; DRUG TOLERABILITY; DRUG TREATMENT FAILURE; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; INCIDENCE; MACROPHAGE; MAXIMUM PLASMA CONCENTRATION; MICROGLIA; MONOTHERAPY; NONHUMAN; PATHOPHYSIOLOGY; PHARMACODYNAMICS; PLASMA HALF LIFE; PREVALENCE; PRIMARY PREVENTION; PRIORITY JOURNAL; REVIEW; RISK FACTOR; SINGLE DRUG DOSE; TREATMENT OUTCOME; UNSPECIFIED SIDE EFFECT; VIRUS MUTATION; VIRUS PATHOGENESIS; VIRUS RESISTANCE;

AIDS DEMENTIA COMPLEX; ANIMALS; ANTIRETROVIRAL THERAPY, HIGHLY ACTIVE; HIV INFECTIONS; HIV-1; HUMANS;

EID: 38949182568     PISSN: 15748898     EISSN: None     Source Type: Journal    
DOI: 10.2174/157488908783421438     Document Type: Review

References (151)

1. Mattson MP, Haughey NJ, Nath A. Cell death in HIV dementia. Cell Death and Differentiation 2005; 12:893-904. Review.
2. Muesing MA, Smith DH, Cabradilla CD, Benton CV, Lasky LA, Capon DJ. Nucleic acid structure and expression of the human AIDS/lymphadenopathy retrovirus. Nature 1985; 313:450-458.
3. Wain-Hobson S, Alizon M, Montagnier L. Relationship of AIDS to other retroviruses. Nature 1985; 313:743.
4. Kramer-Hammerle S, Rothenaigner I, Wolff H, Bell JE, Brack-Werner R. Cells of the central nervous system as targets and reservoirs of the human immunodeficiency virus. Virus Res 2005; 111:194-213.
5. Peluso R, Haase A, Stowring L, Edwards M, Ventura P. A Trojan Horse mechanism for the spread of visna virus in monocytes. Virology 1985; 147: 231-236.
6. Verani A, Gras G, Pancino G. Macrophages and HIV-1: dangerous liaisons. Mol Immunol 2005; 42:195-212.
7. Kim WK, Corey S, Alvarez X, William K. Monocyte/macrophage traffic in HIV and SIV encephalitis.J Leukoc Biol 2003; 74:650-656.
8. Weiss JM, Nath A, Major EO, Berman JW. HIV-1 Tat induces monocyte chemoattractant protein-1-mediated monocyte transmigration across a model of the human blood-brain barrier and up-regulates CCR5 expression on human monocytes. J Immunol 1999; 163:2953-2959.
9. Pu H, Tian J, Flora G, et al. HIV-1 Tat protein upregulates inflammatory mediators and induces monocyte invasion into the brain. Mol Cell Neurosci 2003; 24:224-37.
10. D'Aversa TG, Yu KO, Berman JW. Expression of chemokines by human fetal microglia after treatment with the human immunodeficiency virus type 1 protein Tat. J Neurovirol 2004; 10:86-97.
11. Ryan LA, Cotter RL, Zink WE, Gendelman BE, Zheng J. Macrophages, chemokines and neuronal injury in HIV-1-associated dementia. Cell Mol Biol (Noisy-le-grand) 2002; 48:137-150. Review.
12. D'Aversa TG, Weidenheim KM, Berman JW. CD40-CD40L interactions induce chemokine expression by human microglia: implications for human immunodeficiency virus encephalitis and multiple sclerosis. Am J Pathol 2002; 160:559-567.
13. Banks VA, Abba JK. Adsorptive endocytosis mediates the passage of HIV-1 across the blood-brain barrier: evidence for a post-internalization coreceptor. J Cell Sci 1998; 111: 533-540
14. Banks WA, Freed EO, Wolf KM, Robinson SM, Franko M, Kumar VB. Transport of human immunodeficiency virus type 1 pseudoviruses across the blood-brain barrier: role of envelope proteins and adsorptive endocyto$is. J Virol 2001; 75:4681-4691.
15. Kaul M, Zheng J, Okamoto S, Gendelman HE, Lipton SA. HIV-1 infection and AIDS: consequences for the central nervous system. Cell Death Differ 2005; 12:878-892.
16. Boven LA, van der Bruggen T, Sweder van Asbeck B, Marx JJ, Nottet HS. Potential role of CCR5 polymorphism in the development of AIDS dementia complex. FEMS Immunol Med Microbiol 1999; 26:243-247.
17. Panek RB, Benveniste EN. Class II MHC gene expression in microglia. Regulation by the cytokines IFN-gammia, TNFalpha, and TGF-beta. J Immunol 1995; 154:2846-2854.
18. Wilt SG, Milward E, Zhou JM, et al. in vitro Evidence for a dual role of tumor necrosis factor-alpha in human immunodeficiency virus type 1 encephalopathy. Ann Neurol 1995; 37:381-394.
19. Wesselingh SL, Takahashi K, Glass JD, McArthur JC, Griffin JW, Griffin DE. Cellular localization of tumor necrosis factor mRNA in neurological tissue from HIV-infected patients by combined reverse transcriptase/ polymerase chain reaction in situ hybridization and immunohistochemistry.J Neuroimmunol 1997; 74:1-8.
20. Fiala M, Rhodes RH, Shapshak P, et al. Regulation of HIV-1 infection in astrocytes: expression of Nef, TNF-alpha and IL-6 is enhanced in coculture of astrocytes with macrophages. J Neurovirol 1996; 2:158-166.
21. Yoshioka M, Bradley WG, Shapshak P, et al. Role of immune activation and cytokine expression in HIV-1-associated neurologic diseases. Adv Neuroimmunol. 1995; 5:335-358.
22. Griffin DE. Cytokines in the brain during viral infection: clues to HIV-associated dementia. J Clin Invest 1997; 100:2948-2951.
23. Smith DG, Guillemin GJ, Pemberton L, et al. Quinolinic acid is produced by macrophages stimulated by platelet activating factor, Nef and Tat. J Neurovirol 2001;7:56-60.
24. Valle K Price RW, Nilsson A, Heyes K Verotta D. CSF quinolinic acid levels are determined by local HIV infection: cross-sectional analysis and modelling of dynamics following antiretroviral therapy. Brain 2004; 127:1047-1060.
25. Heyes MP, Ellis RJ, Ryan L, et al. ENRC Group. HIV Neurobehavioral Research Center. Elevated cerebrospinal fluid quinolinic acid levels are associated with region-specific cerebral volume loss in HIV infection. Brain 2001; 124:1033-1042.
26. Pemberton LA, Kerr SJ, Smythe G, Brew BJ. Quinolinic acid production by macrophages stimulated with IFN-gamma, TNF-alpha, and IFN-alpha. J Interferon Cytokine Res 1997; 17:589-595.
27. Brewer C, Bonin F, Bullock P, et al. Platelet activating factor-induced apoptosis is inhibited by ectopic expression of the platelet activating factor G-protein coupled receptor. J Neurochem 2002; 82:1502-1511.
28. Genis P, Jett K Bernton EW, et al. Cytokines and arachidonic metabolites produced during human immunodeficiency virus (HIV)-infected macrophage-astroglia interactions: implications for the neuropathogenesis of HIV disease. J Exp Med 1992; 176:1703-1718.
29. Perry SW, Hamilton JA, Tjoelker LW, et al. Platelet-activating factor receptor activation. An initiator step in HIV-1 neuropathogenesis. J Biol Chem 1998; 273:17660-17664.
30. Garden GA. Microglia in human immunodeficiency virus-associated neurodegeneration. Glia 2002; 40:240-251.
31. Mollace V, Nottet HS, Clayette P, et al. Oxidative stress and neuroAIDS: triggers, modulators and novel antioxidants. Trends Neurosci 2001; 24:411-416.
32. Adamson DC, Wildemann B, Sasaki K et al. Immunologic NO synthase: elevation in severe AIDS dementia and induction by HIV-1 gp41. Science 1996; 274:1917-1921.
33. Minagar A, Shapshak P, Fujimura R, Ownby R, Heyes M, Eisdorfer C. The role of macrophage/microglia and astrocytes in the pathogenesis of three neurologic disorders: HIV-associated dementia, Alzheimer disease, and multiple sclerosis. J Neurol Sci 2002; 202:13-23.
34. Kedzierska K, Crowe SM. The role of monocytes and macrophages in the pathogenesis of HIV-1 infection. Curr Med Chem 2002; 9:1893-1903.
35. Balestra E, Perno CF, Aquaro S, et al. Macrophages: a crucial reservoir for human immunodeficiency virus in the body. J Biol Regul Homeost Agents 2001; 15:272-276.
36. Lambotte O, Taoufik Y, de Goer 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.
37. Meltzer MS, Nakamura M, Hansen BD, Turpin JA, Kalter DC, Gendelman HE. Macrophages as susceptible targets for HIV infection, persistent vital reservoirs in tissue, and key immunoregulatory cells that control levels of virus replication and extent of disease. AIDS Res Hum Retroviruses 1990; 6:967-971.
38. Garaci E, Caroleo MC, Aloe L, et al. Nerve growth factor is an autocrine factor essential for the survival of macrophages infected with HIV. Proc Natl Acad Sci USA 1999; 96:14013-14018.
39. Huber JD, Egleton RD, Davis TP. Molecular physiology and pathophysiology of tight junctions in the blood-brain barrier. Trends Neurosci 2001; 24:719-725.
40. Pieper GK Olds CL, Bub JD, Lindholm PF. Transfection of human endothelial cells with HIV-1 tat gene activates NF-kappa B and enhances monocyte adhesion. Am J Physiol Heart Circ Physiol 2002; 283:H2315-21.
41. Cioni C, Annunziata P. Circulating gp120 alters the blood-brain barrier permeability in HIV-1 gp120 transgenic mice. Neurosci Lett 2002, 330:299-301
42. Toneatto S, Finco O, van der Putten H, Abrignani S, Annunziata P. Evidence of blood-brain barrier alteration and activation in HIV-1 gp120 transgenic mice. AIDS 1999; 13:2343-2348.
43. Cicala C, Arthos J, Selig SM, et al. HIV envelope induces a cascade of cell signals in non-proliferating target cells that favor virus replication. Proc Natl Acad Sci USA 2002; 99:9380-9385.
44. Didier N, Banks WA, Creminon C, Dereuddre-Bosquet N, Mabondzo A. HIV-1-induced production of endothelin-1 in an in vitro model of the human blood-brain barrier. Neuroreport 2002; 13:1179-1183.
45. McMillen MA, Huribal M, Cunningham ME, Kumar R, Sumpio BE. Endothelin-1 increases intracellular calcium in human monocytes and causes production of interleukirn-6. Crit Care Med 1995; 23:34-40.
46. Ehrenreich H, Rieckmann P, Sinowatz F, et al. Potent stimulation of monocytic endothelin-1 production by HIV-1 glycoprotein 120. J Immunol 1993; 150:4601-4609.
47. Chen P, Mayne M, Power C, Nath A. The Tat protein of HIV-1 induces tumor necrosis factor-alpha production. Implications for HIV-1 -associated neurological diseases. J Biol Chem 1997; 272:22385-22388.
48. Johnston JB, Zhang K, Silva C, et al. HIV-1 Tat neurotoxicity is prevented by matrix metalloproteinase inhibitors. Ann Neurol 2001; 49:230-241.
49. Kumar A, Dhawan S, Mukhopadhyay A, Aggarwal BB. Human immunodeficiency virus-1-tat induces matrix metalloproteinase-9 in monocytes through protein tyrosine phosphatase-mediated activation of nuclear transcription factor NF-kappaB. FEBS Lett 1999; 462:140-144.
50. Sporer B, Koedel U, Paul R, et al. Human immunodeficiency virus type-1 Nef protein induces blood-brain barrier disruption in the rat: role of matrix metalloproteinase-9. J Neuroimmune 2000; 102:125-30.
51. Nottet HSLM, Persidsky Y, Sasseville VG, et al. Mechanisms for the transendothelial migration of HIV-1 infected monocytes into brain. J Immunol 1996; 156:1284-1295.
52. Bachoo RM, Kim RS, Ligon KL, et al. Molecular diversity of astrocytes with implications for neurological disorders. Proc Natl Acad Sci USA 2004; 101:8384-8389.
53. Davies DL, Niesman IR, Boop FA, Phelan KD. Heterogeneity of astroglia cultured from adult human temporal lobe. Int J Dev Neurosci 2000; 18:151-160.
54. Danbolt NC. Glutamate uptake.Prog Neurobiol 2001; 65:1-105.
55. Fields RD, Stevens-Graham B. New insights into neuron-glia communication. Science 2002; 298:556-562.
56. Bezzi P, Volterra A. A neuron-glia signalling network in the active brain. Curr Opin Neurobiol 2001; 11:387-394.
57. He J, deCastro CM, Vandenbark GR, Busciglio J, Gabuzda D. Astrocyte apoptosis induced by HIV-1 transactivation of the c-kit protooncogene. Proc Natl Acad Sci USA 1997; 94:3954-3959.
58. Zheng J, Ghorpade A, Niemana D, et al. Lymphotropic virions affect chemokine receptor-mediated neural signaling andapoptosis: implications for human immunodeficiency virus type 1-associated dementia. J Virol 1999; 73:8256-8267.
59. Dou H, Morehead J, Bradley J, et al. Neuropathologic and neuroinflammatory activities of HIV-1-infected human astrocytes in murine brain. Glia 2006; 54:81-93.
60. Saito Y, Sharer LR, Epstein LG, et al. Overexpression of NEF as a marker for restricted HIV-1 infection of astrocytes in postmortem pediatric central nervous tissues. Neurology 1994; 44:474-481.
61. Tomatore C, Chandra It, Berger JR, Major EO. HIV-1 infection of subcortical astrocytes in the pediatric central nervous system. Neurology 1994; 44:481-487.
62. Ranki A, Nyberg K Ovod V, et al. Abundant expression of HIV Nef and Rev proteins in brain astrocytes in vivo is associated with dementia. AIDS 1995; 9: 1001-1008.
63. Gorry PR, Ong C, Thorpe J, et al. Astrocyte infection by HIV-1: mechanisms of restricted virus replication, and role in the pathogenesis of HIV-1-associated dementia. Curr HIV Res 2003; 1:463-473.
64. Brack-Werner R. Astrocytes. HIV cellular reservoirs and important participants in neuropathogenesis. AIDS 1999; 13:1-22.
65. Dong Y, Benveniste EN. Immune function of astrocytes. Glia. 2001; 36:180-190.
66. Ghafouri M, Amini S, Khalili K, Sawaya BE. HIV-1 associated dementia: symptoms and causes. Retrovirology 2006; 3:28.
67. Elovaara I, Sabri F, Gray F, Alafuzoff I, Chiodi F. Upregulated expression of Fas and Fas ligand in brain through the spectrum of HIV-1 infection. Acta Neuropathol (Berl) 1999; 98:355-362.
68. Sabri F, De Milito A, Pirskanen R, et al. Elevated levels of soluble FSA and FAS ligand in cerebrospinal fluid of patients with AIDS dementia complex. J Neuroimmunol 2001; 114:197-206.
69. Mueller YM, De Rosa SC, Hutton JA, et al. Increased CD95/ FAS-induced apeptosis of HIV-specific CD8(+) T cells. Immunity 2001; 15:871-882
70. Dockrell DH, Badley AD, Villacian JS, et al. The expression of FAS Ligand by macrophages and its upregulation by human immunodeficiency virus infection. J Clin Invest 1998; 101:2394-2405.
71. Aquaro S, Panti S, Caroleo MC, et al. Primary macrophages infected by human immunodeficiency virus trigger CD95-mediated apoptosis of uninfected astrocytes. J Leukoc Biol 2000; 68:429-435.
72. Ghorpade A, Holter S, Borgmann K, Persidsky R, Wu L. HIV-1 and IL-1 beta regulate Fas ligand expression in human astrocytes through the NF-kappa B pathway. Neuroimmunol 2003; 141:141-149.
73. Lavi E, Kolson LD, Ulrich MA, Fu L, González-Scarano F. Chemokine receptors in the human brain and their relationship to HIV infection. J NeuroVirol 1998; 4:301-311.
74. Glabinski AR, Ransohoff RM. Chemokines and chemokine receptors in CNS pathology. J Neurovirol 1999; 5: 3-12.
75. Hesselgesser J, Horuk R. Chemokine and chemokine receptor expression in the central nervous system. J Neurovirol 1999; 5:13-26.
76. Li J, Bentsman G, Potash MJ, Volsky DJ. Human immunodecifiency virus type efficiently binds to human fetal astrocytes and induces neuroinflammatory responses independent of infection. BMC Neurosci 2007; 8:31.
77. Haughey NJ, Mattson MP. Calcium dysregulation and neuronal apoptosis by the HIV-1 proteins Tat and gp120. J Acquir Immune Defic Syndr 2002; 31:S55-61.
78. Nardacci R, Antinori A, Kroemer G, Pincentini M. Cell death mechanisms in HIV-associated dementia: the involvement of syncytia. Cell Death Differ 2005; 12:855-898.
79. Lipton SA. Neuronal injury associated with HIV-1: approaches to treatment. Annu Rev Pharmacol Toxicol 1998; 38:159-177.
80. McArthur JC, Hoover DR, Bacellar H, et al. Dementia in AIDS patients: incidence and risk factors. Multicenter AIDS Cohort Study. Neurology 1993; 43:2245-2252.
81. Langford TD, Letendre SL, Larrea GJ, Masliah E. Changing patterns in the neuropathogenesis of HIV during the HAART era. Brain Pathol 2003; 13:195-210.
82. Moroni M, Antinori S. HIV and direct damage of organs: disease spectrum before and during the highlyactive antiretroviral therapy era. AIDS 2003; 17:S51-64.
83. Sperber K, Shao L. Neurologic consequences of HIV infection in the era of HAART. AIDS Patient Care STDS. 2003; 17:509-518.
84. Brew BJ. Evidence for a change in AIDS dementia complex in the era of highly active antiretroviral therapy and the possibility of new forms of AIDS dementia complex. AIDS 2004; 18:S75-78.
85. Sacktor N, Tarwater PM, Skolasky RL, et al. Multicenter for AIDS Cohort Study (MACS). CSF antiretroviral drug penetrance and the treatment of HIV-associated psychomotor slowing. Neurology 2001; 57:542-544.
86. Dore GJ, Hoy JF, Mallal SA, et al. Trends in incidence of AIDS illnesses in Australia from 1983 to 1994: the Australian AIDS cohort. J Acquir Immune Defic Syndr Hum Retrovirol 1997; 16:39-43.
87. Ferrando S, van Gorp W, McElhiney M, Goggin K, Sewell M, Rabkin J. Highly active antiretroviral treatment in HIV infection: benefits for neuropsychological function. AIDS 1998; 12:F65-70.
88. Enting RH, Hoetelmans RMW, Lange JMA, Burger DM, Beijnen JH, Portogies P. Antiretroviral drugs and the central nervous system. AIDS 1998; 12:1941-1955
89. Smit TK, Brew BJ, Tourtellotte W, Morgello S, Gelman BB, Saksena NK. Independent evolution of human immunodeficiency virus (HIV) drug resistance mutations in diverse areas of the brain in HIV-infected patients, with and without dementia, on antiretroviral treatment. J Virol 2004; 18:10133-10148.
90. Cunningham PH, Smith DG, Satchell C, Cooper DA, Brew B. Evidence for independent development of resistance to HIV-1 reverse transcriptase inhibitors in the cerebrospinal fluid. AIDS 2000; 14:1949-1954.
91. Weidenheim KM, Epshteyn I, Lyman WD. Immunocytochemical identification of T-cells in HIV-1 encephalitis: implications for pathogenesis of CNS disease.Mod Pathol 1993; 6:167-174.
92. von Herrath M, Oldstone MB, Fok HS. Simian immunodeficiency virus (SIV)-specific CTL in cerebrospinal fluid and brains of SIV-infected rhesus macaques. J Immunol 1995; 154:5582-5589.
93. Shaw GM, Harper ME, Hahn BH, et al. HTLV-III infection in brains of children and adults with AIDS encephalopathy. Science 1985; 227:177-182.
94. Gabuzda DH, Ho DD, de la Monte SM, Hirsch MS, Rota TR, Sobel RA. Immunohistochemical identification of HTLV-III antigen in brains of patients with AIDS. Ann Neurol 1996; 20:289-295.
95. Koenig S, Gendelman HE, Orenstein JM, et al. Detection of AIDS virus in macrophages in brain tissue from AIDS patients with encephalopathy. Science 1986; 233:1089-1093.
96. Peudenier S, Hery C, Montagnier L, Tardieu M. Human microglial cells: characterization in cerebral tissue and in primary culture, and study of their susceptibility to HIV-1 infection. Ann Neurol 1991; 29:152-161.
97. Takahashi K, Wesselingh SL, Griffin DE, McArthur JC, Johnson RT, Glass JD. Localization of HIV-1 in human brain using polymerase chain reaction/ in situ hybridization and immunocytochemistry. Ann Neurol 1996; 39:705-711.
98. Jones MV, Bell JE, Nath A. Immunolocalization of HIV envelope gp120 in HIV encephalitis with dementia. AIDS 2000; 14:2709-2713.
99. Igarashi T, Brown CR, Endo Y, et al. Macrophage are the principal reservoir and sustain high virus loads in rhesus macaques after the depletion of CD4+ T cells by a highly pathogenic simian immunodeficiency virus/HIV type 1 chimera (SHIV): implications for HIV-1 infections of humans. Proc Natl Acad Sci USA 2001; 98:658-663.
100. Aleman S, Söderbärg K, Visco-Cómandini U, Sitbon G, Sönnerborg A. Drug resistance at low viraemia in HIV-1-infected patients with antiretroviral combination therapy. AIDS 2002; 16:1039-1044.
101. Stellbrink HJ, van Lunzen J, Hufert FT, et al. Asymptomatic HIV infection is characterized by rapid turnover of HIV RNA in plasma and lymph nodes but not of latently infected lymph-node CD4+ T cells. AIDS 1997; 11:1103-1110.
102. Kepler TB, Perelson AS. Drug concentration heterogeneity facilitates the evolution of drug resistance. Proc Natl Acad Sci USA 1998; 29:11514-11519.
103. Lipton SA. Treating AIDS dementia. Science 1997; 276:1629-1630.
104. Antinori A, Cingolani A, Giancola ML, Forbici F, De Luca A, Perno CF. Clinical implications of HIV-1 drug resistance in the neurological compartment. Scand J Infect Dis Suppl 2003; 35:41-44.
105. Cook JE, Dasgupta S, Middaugh LD, et al. Highly active antiretroviral therapy and himan immunodeficiency virus encephalitis. Ann Neurol 2005; 57:795-803.
106. Eggers C, Hertogs K, Stürenburg HJ, van Lunzen J, Stellbrink HJ. Delayed central nervous system virus suppression during highly active antiretroviral therapy is associated with HIV encephalopathy, but not with vital drug resistance or poor central nervous system drug penetration. AIDS 2003; 17:1897-1906.
107. Thomas SA. Anti-HIV drug distribution to the central nervous system. Curr Pharm Des. 2004; 10: 1313-1324.
108. Drake SM. NNRTIs- a new class of drugs for HIV. J of Antimicrob Chemother 2000; 45:417-420.
109. Gibbs JE, Gaffien Z, Thomas SA. Nevirapine uptake into the central nervous system of the Guinea pig: an in situ brain perfusion study. J Pharmacol Exp Ther 2006; 317:746-751.
110. Nath A, Sacktor N. Influence of highly active antiretroviral therapy on persistence of HIV in the central nervous system. Curr Opin Neurol 2006; 19:358-361.
111. Letendre SL, McCutchan JA, Childers ME, et al. HNRC Group. Enhancing antiretroviral therapy for human immunodeficiency virus cognitive disorders. Ann Nourol 2004; 56:416-423.
112. Sacktor N, Skolasky RL, Tarwater PM, et al. Multicenter AIDS Cohort Study (MACS). Response to systemic HIV viral load suppression correlates with psychomotor speed performance. Neurology 2003; 61:567-569.
113. Van Acker, K.L.A., Temse, B., Wigerinck, P.T.B.P., Lieve E., Tahri, A.: US20070066623A1 (2007).
114. Shah M, Smit TK, Morgello S, et al. Env gp120 sequence analysis of HIV type 1 strains from diverse areas of the brain shows preponderance of CCR5 usage. AIDS Res Hum Retroviruses 2006; 22:177-181
115. Jiang Y, Jolly PE. Effect of beta-chemokines on human immunodeficiency virus type 1 replication, binding, uncoating, and CCR5 receptor expression in human monocyte-derived macrophages. J Hum Virol 1999; 2:123-132.
116. Cocchi F, De Vico AL, Garzino-Demo A, Arya SK, Gallo RC, Lusso P. Identification of RANTES, MIP-1alpha, and MIP-1beta major HIV-suppressive factors produced by CD8+ T cells. Science 1995; 270:1811-1815.
117. Aquaro S, Menten P, Struyf S, et al. The LD78beta isoform of MIP-1α is the most potent CC-chemokine in inhibiting CCR5-dependent HIV-1 replication in human macrophages. J Virol 2001; 75:4402-4406.
118. Dorr P, Westby M, Dobbs S, et al. Maraviroc (UK-427,857), a potent orally bioavailable and selective small-molecule inhibitor of chemokine receptor CCR5 with broad-spectrum anti-human immunodeficiency virus type 1 activity. Antimicrob Agents Chemother 2005; 49:4721-4732.
119. Reeves JD, Piefer AJ. Emerging drug targets for antiretroviral therapy. Drugs 2005; 65.1747-1766.
120. Strizki JM, Tremblay C, Xu S, et al. Discovery and characterization of vicriviroc (SCH 417690), A CCR5 antagonist with potent activity against human immunodeficiency virus type 1. Antimicrob Agents Chemother 2005; 49:4911-4919.
121. Westby M, Van der Ryst E. CCR5 antagonists: host- targeted antivirals for the treatment of HIV infection. Antivir. Chem Chemother 2005; 16:339-354.
122. Walker DK, Abel S, Comby P, Muirhead GJ, Nedderman AN, Smith DA. Species differences in the disposition of the CCR5 antagonist, UK-427,857, a new potential treatment for HIV. Drug Metab Dispos 2005; 33:587-95.
123. Willey S, Peters PJ, Sullivan WM, Dorr P, Perros M, Clapham PR. Inhibition of CCR5-mediated infection by diverse R5 and R5X4 HIV and SIV isolates using novel small molecule inhibitors of CCR5: effects of viral diversity, target cell and receptor density. Antiviral Res 2005; 68:96-108.
124. Baba M, Takashima K, Miyake H, et al. TAK-652 inhibits CCR5-mediated human immunodeficiency virus type 1 infection in vitro and has favorable pharmacokinetics in humans. Antimicrob Agents Chemother 2005; 49:4584-4591.
125. Baritaki S, Dittmar MT, Spandidos DA, Krambovitis E. in vitro Inhibition of R5 HIV-1 infectivity by X4 V3-derived synthetic peptides. Int J Mol Med 2005; 16:333-336.
126. Ruff MR, Polianova M, Yang QE, Leoung GS, Ruscetti FW, Pert CB. Update an D-ala-peptide Tramide (DAPTA): a viral entry inhibitor that blocks CCR5 chemokine receptors. Curr HIV Res 2003; 1:51-67
127. Ruff MR, Melendez-Guerrero LM, Yang QE, et al. Peptide T inhibits HIV-1 infection mediated by the chemokine receptor-5 (CCR5). Antiviral Res 2001; 52:63-75.
128. Pollicita M, Ruff M, Pert CB, et al. Profound anti-HIV-1 activity of DAPTA in monocytes/macrophages and inhibition of CCR5-mediated apoptosis in neuronal cells. Antiviral Chemistry and Chemotherapy 2007; 18:285-295.
129. Trkola A, Ketas TJ, Nagashima KA, et al. Potent, broad-spectrum inhibition of human immunodeficiency virus type 1 by the CCR5 monoclonal antibody PRO 140. J Viiol 2001; 75:579-588.
130. Chen X, Yang L, Zhang N, et al. Shikonin, a component of chinese herbal medicine, inhibits chemokine receptor function and suppresses human immunodeficiency virus type 1. Antimicrob Agents Chemother 2003; 47:2810-2816.
131. Roschke, V., Rosen, C.A., Ruben, S.M.: US20077175988 (2007).
132. Balzarini J, Van Laethem K, Hatse S, et al. Carbohydrate-binding agents cause deletions of highly conserved glycosylation sites in HIV GP120. A new therapeutic concept to hit the Achilles heel of HIV. J Biol Chem 2005; 280:41005-41014.
133. Balzarini J, Hatse S, Venneire K, et al. Mannose-specific plant lectins from the Amaryllidaceae family quality as efficient microbicides for prevention of human immunodeficiency virus infection. Antimicrob Agents Chemother 2004; 48:3858-3870.
134. Balzarini J. Targeting the glycans of gp120: a novel therapeutic approach aimed at the Achilles heel of HIV. Lancet 2005; 5:726-731.
135. Balzarini, J.: WO07033444A2 (2007).
136. Prevelige, P.Jr.: WO07048042C2 (2007).
137. Zhou J, Chen CH, Aiken C. The sequence of the CA-SP1 junction accounts for the differential sensitivity of HIV-1 and SIV to the small molecule maturation inhibitor 3-0-{3′,3′-dimethylsucciny1}-betulinic acid. Retrovirology 2004. 1:15
138. Sakalian M, McMurtrey CP, Deeg FJ, et al. 3-O-(3′,3′ dimethysuccinyl) betulinic acid inhibits maturation of the human immunodeficiency virus type 1 Gag precursor assembled in vitro. J Virol 2006; 80:5716-5722.
139. Adamson CS, Ablan SD, Boeras I, et al. in vitro Resistance to the human immunodeficiency virus type 1 maturation inhibitor PA-457 (Bevirimat). J Virol 2006; 80:10957-10971.
140. Zhou J, Chen CH, Aiken C. Human immunodeficiency virus type 1 resistance to the small molecule maturation inhibitor 3-O(3′,3′-dimethylsuccinyl)-betulinic acid is conferred by a variety of single amino Acid substitutions at the CA-SP1 cleavage site in Gag. J Virol 2006; 80:12095-12101.
141. Li F, Goila-Gaur R, Salzwedel K, et al. PA-457: a potent HIV inhibitor that disrupts core condensation by targeting a late step in Gag processing. Proc Natl Acad Sci USA 2003; 100:13555-60.
142. Malet J, Wirden M, Derache A, et al. Primary genotypic resistance of HIV-1 to the maturation inhibitor PA-457 in protease inhibitor- experienced patients. AIDS 2007; 21:871-873.
143. Martin DE, Blum R, Doto J, Galbraith H,, Ballow C. Multiple-dose pharmacokinetics and safety of bevirimat, a novel inhibitor of HIV maturation, in healthy volunteers. Clin Pharmacokinet 2007; 46:589-598.
144. Martin DE, Blum R, Wilton J, et al. Safety and Pharmacokinetics of Bevirimat (PA-457), a Novel Inhibitor of Human Immunodeficiency Virus Maturation, in Healthy Volunteers. Antimicrob Agents Chemother 2007; 51:3063-3066.
145. Smith PF, Ogundele A, Forrest A, et al. Phase I/II study of the safety, virologic effect, and pharmacokinetics/pharmacodynamics of single dose 3-O-(3′,3′-dimethylsuccinyl) betulinic acid (Bevirimat) in HIV-infection. antimicrob agents. Chemother 2007. Epub ahead of print
146. Aquaro S, Svicher V, Schols D, et al. Mechanisms underlying activity of antiretroviral drugs in HIV-1-infected macrophages: new therapeutic strategies. J Leukoc Biol 2006; 80:1103-1110.
147. Naidu, B.N., Ueda, Y., Matiskella, J.D., Walker, M.A., Banville, J., Beaulieu, F., Ouellet, C., Plamondon, S.: US20070111984A1 (2007).
148. Shor-Posner G, Lecusay R, Morales G, Campa A, Miguez-Burbano MJ. Neuroprotection in HIV-posilive drug users: implications for antioxidant therapy. J Acquir Immune Defic Syndr 2002; 31:S84-88.
149. Turchan J, Sacktor N, Wojna V, Conant K, Nath A. Neuroprotective therapy for HIV dementia. Curr HIV Res 2003; 1:373-383.
150. Bjugstad KB, Flitter WD, Garland WA, Su GC, Arendash GW. Preventive actions of a synthetic antioxidant in a novel animal model of AIDS dementia. Brain Res 1998; 795:349-357.
151. Koutsilieri E, ter Meulen V, Riedeier P. Neurotransmission in HIV associated dementia: a short review. J Neural Transm 2001; 108:767-775.