Global Issues in Neuro-AIDS and Their Evolution over the Future of the HAART Era

Bruce J. Brew

doi:10.1128/9781555815691.ch36

Chapter 36 : Global Issues in Neuro-AIDS and Their Evolution over the Future of the HAART Era

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Affiliations: 1: Departments of Neurology, HIV Medicine, Centre for Immunology, and National Centre in HIV Epidemiology and Clinical Research, St. Vincent’s Hospital, University of New South Wales, Sydney 2010, Australia

Content Type: Monograph

Publication Year: 2009

Category: Viruses and Viral Pathogenesis

Book DOI: 10.1128/9781555815691

Chapter DOI: 10.1128/9781555815691.ch36

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Abstract:

In developed countries the effect of highly active antiretroviral therapy (HAART) on the neurological complications in the short term has been well described, but the long-term effects are only just starting to be clarified. These issues are best discussed within a framework that structures the complications according to whether they are direct or indirect. Within this framework this chapter deals briefly with the more significant aspects of nervous system involvement in HIV infection emphasizing three points: possible new complications in developing countries, new complications in HAART-treated patients as well as complications such as progressive multifocal leukoencephalopathy (PML) that have only marginally changed with HAART, and future directions. The direct complications such as dementia and neuropathy are organized according to the degree of advancement of HIV disease and anatomical region involved. With the introduction of HAART, some aspects of investigations have changed; however, this is an evolving area that still needs clarification. There are several myopathies that have been linked to HIV disease. The association seems to be at least in part causal rather than just associative. The two most important are polymyositis and inclusion body myositis. The indirect neurological complications related to HIV disease are many. Only the more important are discussed in the chapter. The most significant aspects of these disorders in the era of HAART are that the incidence of opportunistic infections has significantly declined with HAART and that HAART may induce the clinical expression of previously subclinical disease through the immune reconstitution syndrome.

Citation: Brew B. 2009. Global Issues in Neuro-AIDS and Their Evolution over the Future of the HAART Era, p 507-523. In Goodkin K, Shapshak P, Verma A (ed), The Spectrum of Neuro-AIDS Disorders. ASM Press, Washington, DC. doi: 10.1128/9781555815691.ch36

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References

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1. Achim, C. L.,, D. A. Green,, M. Avramut,, J. Schindelar,, D. Knight, and, E. Masliah. 2004. Axonal degeneration in the HIV brain. J. Neurovirol. 10 (Suppl. 3) : S60.

2. Adle-Biassette, H.,, F. Chretien,, L. Wingertsmann,, C. Hery,, T. Ereau,, F. Scaravilli,, M. Tardieu, and, F. Gray. 1999. Neuronal apoptosis does not correlate with dementia in HIV infection but is related to microglial activation and axonal damage. Neuropathol. Appl. Neurobiol. 25: 123– 133.

3. Anthony, I. C.,, S. Ramage,, F. W. Brannan, and, J. E. Bell. 2004. Premature neurodegeneration, inflammation and opiate misuse in HIV/AIDS before and after HAART. J. Neurovirol. 10 (Suppl. 3) : S52.

4. Antinori, A.,, G. Arendt,, J. T. Becker,, B. J. Brew,, D. A. Byrd,, M. Cherner,, D. B. Clifford,, P. Cinque,, L. G. Epstein,, K. Goodkin,, M. Gisslen,, I. Grant,, R. K. Heaton,, J. Joseph,, K. Marder,, C. M. Marra,, J. C. McArthur,, M. Nunn,, R. W. Price,, L. Pulliam,, K. R. Robertson,, N. Sacktor,, V. Valcour, and, V. E. Wojna. 2007. Updated research nosology for HIV-associated neurocognitive disorders. Neurology 69: 1789– 1799.

5. Apoola, A.,, S. Ahmad, and, K. Radcliffe. 2002. Primary HIV infection. Int. J. STD AIDS 13: 71– 78.

6. Aquaro, S.,, C. F. Perno,, E. Balestra,, J. Balzarini,, A. Cenci,, M. Francesconi,, S. Panti,, F. Serra,, N. Villani, and, R. Calio. 1997. Inhibition of replication of HIV in primary monocyte/macrophages by different antiviral drugs and comparative efficacy in lymphocytes. J. Leukoc. Biol. 62: 138– 143.

7. Araujo, A.,, and W. W. Hall. 2004. Human T-lymphotropic virus type II and neurological disease. Ann. Neurol. 56: 10– 19.

8. Azzoni, L.,, E. Papasavvas,, J. Chehimi,, J. R. Kostman,, K. Mounzer,, J. Ondercin,, B. Perussia, and, L. J. Montaner. 2002. Sustained impairment of IFN-gamma secretion in suppressed HIV-infected patients despite mature NK cell recovery: evidence for a defective reconstitution of innate immunity. J. Immunol. 168: 5764– 5770.

9. Baba, H.,, T. P. Doubell, and, C. J. Woolf. 1999. Peripheral inflammation facilitates Abeta fiber-mediated synaptic input to the substantia gelatinosa of the adult rat spinal cord. J. Neurosci. 19: 859– 867.

10. Bacellar, H.,, A. Munoz,, E. N. Miller,, B. A. Cohen,, D. Besley,, O. A. Selnes,, J. T. Becker, and, J. C. McArthur. 1994. Temporal trends in the incidence of HIV-1-related neurologic diseases: Multicenter AIDS Cohort Study 1985–1992. Neurology 44: 1892– 1900.

11. Bachis, A.,, E. O. Major, and, I. Mocchetti. 2003. Brain-derived neurotrophic factor inhibits human immunodeficiency virus-1/gp120-mediated cerebellar granule cell death by preventing gp120 internalization. J. Neurosci. 23: 5715– 5722.

12. Bagasra, O.,, E. Lavi,, L. Bobroski,, K. Khalili,, J. P. Pestaner,, R. Tawadros, and, R. J. Pomerantz. 1996. Cellular reservoirs of HIV-1 in the central nervous system of infected individuals: identification by the combination of in situ polymerase chain reaction and immunochemistry. AIDS 10: 573– 586.

13. Bell, J. E.,, A. Busuttil,, J. W. Ironside,, S. Rebus,, Y. K. Donaldson,, P. Simmonds, and, J. F. Peutherer. 1993. Human immunodeficiency virus and the brain: investigation of virus load and neuropathologic changes in pre-AIDS subjects. J. Infect. Dis. 168: 818– 824.

14. Biggar, R. J.,, B. K. Johnson,, S. S. Musoke,, J. B. Masembe,, D. M. Silverstein,, M. M. Warshow, and, S. Alexander. 1986. Severe illness associated with the appearance of antibody to human immunodeficiency virus in an African. Br. Med. J. 293: 1210– 1211.

15. Boufassa, F.,, C. Bachmeyer,, C. Carne,, C. Deveau,, A. Persoz,, C. Jadand,, D. Sereni,, D. Bucquet, et al. 1995. Influence of neurologic manifestations of primary human immunodeficiency virus infection on disease progression. J. Infect. Dis. 171: 1190– 1195.

16. Bouwman, F. H.,, R. Skolasky,, D. Hes,, O. A. Selnes,, J. D. Glass,, T. E. Nance-Sproson,, W. Royal,, G. J. Dal Pan, and, J. C. McArthur. 1998. Variable progression of HIV-associated dementia. Neurology 50: 1814– 1820.

17. Brannagan, T. H.,, G. J. Nuovo,, A. P. Hays, and, N. Latov. 1997. Human immunodeficiency virus infection of dorsal root ganglion neurons detected by polymerase chain reaction in situ hybridization. Ann. Neurol. 42: 368– 372.

18. Brew, B. J. 2001a. AIDS dementia complex, p. 74–77. In B. J. Brew (ed.), HIV Neurology. Oxford University Press, New York, NY.

19. Brew, B. J. 2001b. Cerebrovascular complications and transient neurologic deficits, p. 146– 151. In B. J. Brew (ed.), HIV Neurology. Oxford University Press, New York, NY.

20. Brew, B. J. 2001c. Cryptococcal meningitis, p. 91– 96. In B. J. Brew (ed.), HIV Neurology. Oxford University Press, New York, NY.

21. Brew, B. J. 2001d. Toxoplasmosis, p. 117– 123. In B. J. Brew (ed.), HIV Neurology. Oxford University Press, New York, NY.

22. Brew, B. J. 2001e. Uncommon causes of nonfocal brain disorders in advanced HIV disease, p. 101– 104. In B. J. Brew (ed.), HIV Neurology. Oxford University Press, New York, NY.

23. Brew, B. J. 2001f. Progressive multifocal leukoencephalopathy, p. 132– 141. In B. J. Brew (ed.), HIV Neurology. Oxford University Press, New York, NY.

24. Brew, B. J. 2003. The peripheral nerve complications of human immunodeficiency virus (HIV) infection. Muscle Nerve 28: 542– 552.

25. Brew, B. J. 2004. Evidence for a change in AIDS dementia complex (ADC) in the era of highly active antiretroviral therapy and the possibility of new forms of ADC. AIDS 18 (Suppl. 1) : S75– S78.

26. Brew, B. J.,, R. B. Bhalla,, M. Paul,, H. Gallardo,, J. C. McArthur,, M. K. Schwartz, and, R. W. Price. 1990. Cerebrospinal fluid concentrations of neopterin in human immunodeficiency virus infection. Ann. Neurol. 28: 556– 560.

27. Brew, B. J.,, R. B. Bhalla,, M. Paul,, J. J. Sidtis,, J. J. Keilp,, A. E. Sadler,, H. Gallardo,, J. C. McArthur,, M. K. Schwartz, and, R. W. Price. 1992. Cerebrospinal fluid β 2 microglobulin in patients with AIDS dementia complex: an expanded series including response to zidovudine treatment. AIDS 6: 461– 465.

28. Brew, B. J.,, L. Evans,, C. Byrne,, L. Pemberton, and, L. Hurren. 1996. The relationship between AIDS dementia complex and the presence of macrophage tropic and non syncytium inducing isolates of human immunodeficiency virus type 1 in the cerebrospinal fluid. J. Neurovirol. 2: 152– 157.

29. Brew, B. J.,, M. Paul,, A. Khan,, M. Gallardo, and, R. W. Price. 1994. Cerebrospinal fluid HIV-1 p24 antigen and culture: sensitivity and specificity for AIDS dementia complex. J. Neurol. Neurosurg. Psychiatry 57: 784– 789.

30. Brew, B. J.,, L. Pemberton,, K. Blennow,, A. Wallin, and, L. Hagberg. 2005. CSF amyloid beta42 and tau levels correlate with AIDS dementia complex. Neurology 65: 1490– 1492.

31. Brew, B. J.,, L. Pemberton,, P. Cunningham, and, M. Law. 1997. Levels of HIV-1 RNA correlate with AIDS dementia. J. Infect. Dis. 175: 963– 966.

32. Brew, B. J.,, M. Perdices,, P. Darveniza,, P. Edwards,, B. Whyte,, W. J. Burke,, R. Garrick,, D. O’Sullivan,, R. Penny, and, D. A. Cooper. 1989. Neurological complications of HIV infection in the absence of immunodeficiency. Aust. N. Z. J. Med. 19: 700– 705.

33. Brew, B. J.,, M. Rosenblum,, K. Cronin, and, R. W. Price. 1995. The AIDS dementia complex and human immunodeficiency virus type 1 brain infection: clinical-virological correlations. Ann. Neurol. 38: 563– 570.

34. Brew, B. J.,, S. Tisch, and, M. Law. 2003. HIV nucleoside neuropathy and HIV distal symmetrical neuropathy: relationships to serum lactate and plasma HIV viral load. AIDS 17: 1094– 1096.

35. Brew, B. J.,, and S. E. Tomlinson. 2004. HIV neuropathy: time for new therapies. Drug Discov. Today Dis. Models 1: 171– 176.

36. Budka, H.,, C. A. Wiley,, P. Kleihues,, J. Artigas,, A. K. Asbury,, E. S. Cho,, D. R. Cornblath,, M. C. Dal Canto,, U. DeGirolami, and, D. Dickson. 1991. HIV-associated disease of the nervous system: review of nomenclature and proposal for neuropathology based terminology. Brain Pathol. 1: 143– 152.

37. Carne, C. A.,, R. S. Tedder,, A. Smith,, S. Sutherland,, S. G. Elkington,, H. M. Daly,, F. E. Preston, and, J. Craske. 1985. Acute encephalopathy coincident with seroconversion for anti-HTLV-III. Lancet ii: 1206– 1208.

38. Cartier, L.,, O. Hartley,, M. Dubois-Dauphin, and, K. H. Krause. 2005. Chemokine receptors in the central nervous system: role in brain inflammation and neurodegenerative diseases. Brain Res. Brain Res. Rev. 48: 16– 42.

39. Castellanos, F.,, J. Mallada,, C. Ricart, and, J. A. Zabala. 1994. Ataxic neuropathy associated with human immunodeficiency virus infection. Arch. Neurol. 51: 236.

40. Centers for Disease Control and Prevention. 2001. U.S. HIV and AIDS cases reported through June 2001. HIV/AIDS Surv. Rep. 13: 1– 44.

41. Chang, L.,, T. Ernst,, M. Leonido-Yee,, I. Walot, and, E. Singer. 1999. Cerebral metabolites correlate with clinical severity of HIV-cognitive motor complex. Neurology 52: 100– 108.

42. Cherry, C. L.,, J. C. McArthur,, J. F. Hoy, and, S. L. Wesselingh. 2003. Nucleoside analogues and neuropathy in the era of HAART. J. Clin. Virol. 26: 195– 207.

43. Childs, E. A.,, R. H. Lyles,, O. A. Selnes,, B. Chen,, E. N. Miller,, B. A. Cohen,, J. T. Becker,, J. Mellors, and, J. C. McArthur. 1999. Plasma viral load and CD4 lymphocytes predict HIV-associated dementia and sensory neuropathy. Neurology 52: 607– 613.

44. Chirenda, J.,, and S. Murugasampillay. 2003. Malaria and HIV co-infection: available evidence, gaps and possible interventions. Cent. Afr. J. Med. 49: 66– 71.

45. Cinque, P.,, L. Vago,, M. Mengozzi,, V. Torri,, D. Ceresa,, E. Vicenzi,, P. Transidico,, A. Vagani,, S. Sozzani,, A. Mantovani,, A. Lazzarin, and, G. Poli. 1998. Elevated cerebrospinal fluid levels of monocyte chemotactic protein-1 correlate with HIV-1 encephalitis and local viral replication. AIDS 12: 1327– 1332.

46. Clark, S. J.,, M. S. Saag,, W. D. Decker,, S. Campbell-Hill,, J. L. Roberson,, P. J. Veldkamp,, J. C. Kappes,, B. H. Hahn, and, G. M. Shaw. 1991. High titers of cytopathic virus in plasma of patients with symptomatic primary HIV-1 infection. N. Engl. J. Med. 324: 954– 960.

47. Conant, K.,, J. C. McArthur,, D. E. Griffin,, L. Sjulson,, L. M. Wahl, and, D. N. Irani. 1999. Cerebrospinal fluid levels of MMP-2, 7 and 9 are elevated in association with human immunodeficiency virus dementia. Ann. Neurol. 46: 391– 398.

48. Cunningham, P.,, D. Smith,, C. Satchell,, D. A. Cooper, and, B. J. Brew. 2000. Evidence for independent development of reverse transcriptase inhibitor resistance patterns in the cerebrospinal fluid. AIDS 14: 1949– 1954.

49. Cupler, E. J.,, M. Leon-Monzon,, J. Miller,, C. Semino-Mora,, T. L. Anderson, and, M. C. Dalakas. 1996. Inclusion body myositis in HIV-1 and HTLV-1 infected patients. Brain 119 (Pt. 6) : 1887– 1893.

50. Cutler, R. G.,, N. J. Haughey,, A. Tammara,, J. C. McArthur,, A. Nath,, R. Reid,, D. L. Vargas,, C. A. Pardo, and, M. P. Mattson. 2004. Dysregulation of sphingolipid and sterol metabolism by ApoE4 in HIV dementia. Neurology 63: 626– 630.

51. Cysique, L. A.,, B. J. Brew,, M. Halman,, J. Catalan,, N. Sacktor,, R. W. Price,, S. Brown,, J. H. Atkinson,, D. B. Clifford,, D. Simpson,, G. Torres,, C. Hall,, C. Power,, K. Marder,, J. C. McArthur,, W. Symonds, and, C. Romero. 2005. Undetectable cerebrospinal fluid HIV RNA and beta-2 microglobulin do not indicate inactive AIDS dementia complex in highly active antiretroviral therapy-treated patients. J. Acquir. Immune Defic. Syndr. 39: 426– 429.

52. Cysique, L. A.,, P. Maruff, and, B. J. Brew. 2004a. Antiretroviral therapy in HIV infection: are neurologically active drugs important? Arch. Neurol. 61: 1699– 1704.

53. Cysique, L. A.,, P. Maruff, and, B. J. Brew. 2004b. 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.

54. Dalakas, M. C.,, and G. H. Pezeshkpour. 1998. Neuromuscular diseases associated with human immunodeficiency virus infection. Ann. Neurol. 23: S38– S48.

55. Dal Pan, G. J.,, J. H. McArthur,, E. Aylward,, O. A. Selnes,, T. E. Nance-Sproson,, A. J. Kumar,, E. D. Mellits, and, J. C. McArthur. 1992. Patterns of cerebral atrophy in HIV-1-infected individuals: results of a quantitative MRI analysis. Neurology 42: 2125– 2130.

56. Dal Pan, J.,, J. D. Glass, and, J. C. McArthur. 1994. Clinicopathological correlations of HIV-1 associated vacuolar myelopathy: an autopsy based case control study. Neurology 44: 2159– 2164.

57. Denning, D. W.,, J. Anderson,, P. Rudge, and, H. Smith. 1987. Acute myelopathy associated with primary infection with human immunodeficiency virus. Br. Med. J. 294: 143– 144.

58. Desquilibet, L.,, C. Goujard,, C. Rouzioux,, M. Sinet,, C. Deveau,, M.-L. Chaix,, D. Sereni,, F. Boufassa,, J.-F. Delfraissy,, L. Meyer, and the PRIMO and SEROCO study groups. 2004. Does transient HAART during primary HIV-1 infection lower the virological set-point ? AIDS 18: 2361– 2369.

59. Di Rocco, A.,, P. Werner,, T. Bottiglieri,, J. Godbold,, M. Liu,, M. Tagliati,, A. Scarano, and, D. Simpson. 2004. Treatment of AIDS-associated myelopathy with L-methionine: a placebo-controlled study. Neurology 63: 1270– 1275.

60. Dore, G.,, P. Correll,, J. Kaldor, and, B. J. Brew. 1999. Changes to the natural history of AIDS dementia complex in the era of HAART. AIDS 13: 1249– 1253.

61. Dore, G. J.,, J. F. Hoy,, S. A. Mallal,, Y. Li,, A. M. Mijch,, M. A. French,, D. A. Cooper, and, J. M. Kaldor. 1997. Trends in incidence of AIDS illnesses in Australia from 1983 to 1994: The Australian AIDS Cohort. J. Acquir. Immune Defic. Syndr. 6: 39– 43.

62. Dore, G. J.,, A. McDonald,, Y. Li,, J. Kaldor, and, B. J. Brew. 2003. Marked improvement in survival following AIDS dementia complex in the era of highly active antiretroviral therapy. AIDS 17: 1539– 1545.

63. Elder, G.,, M. Dalakas,, G. Pezeshkpour, and, J. Sever. 1986. Ataxic neuropathy due to ganglioneuritis after probable acute human immunodeficiency virus infection. Lancet ii: 1275– 1276.

64. Esiri, M. M.,, S. C. Biddolph, and, C. S. Morris. 1998. Prevalence of Alzheimer plaques in AIDS. J. Neurol. Neurosurg. Psychiatry 65: 29– 33.

65. Esiri, M. M.,, and C. S. Morris. 1996. The cellular basis of HIV infection of the CNS and the AIDS dementia complex: oligodendrocyte, p. 133–160. In R. W. Price and, J. J. Sidtis (ed.), The Cellular Basis of Central Nervous System HIV-1 Infection and the AIDS Dementia Complex. Haworth Press, Philadelphia, PA.

66. Estanislao, L.,, K. Carter,, J. McArthur,, R. Olney,, D. Simpson, and the Lidoderm-HIV Neuropathy Group. 2004. A randomized controlled trial of 5% lidocaine gel for HIV-associated distal symmetric polyneuropathy. J. Acquir. Immune Defic. Syndr. 37: 1584– 1586.

67. Famularo, G.,, S. Moretti,, S. Marcellini,, V. Trinchieri,, S. Tzantzoglou,, G. Santini,, A. Longo, and, C. de Simone. 1997. Acetyl-carnitine deficiency in AIDS patients with neurotoxicity on treatment with antiretroviral nucleoside analogues. AIDS 11: 185– 190.

68. Fine, S. M.,, R. A. Angel,, S. W. Perry,, L. G. Epstein,, J. D. Rothstein,, S. Dewhurst, and, H. A. Gelbard. 1996. Tumor necrosis factor α inhibits glutamate uptake by primary human astrocytes: implications for pathogenesis of HIV-1 dementia. J. Biol. Chem. 271: 15303– 15306.

69. Forloni, G.,, F. Demicheli,, S. Giorgi,, C. Bendotti, and, N. Angeretti. 1992. Expression of amyloid precursor protein mRNAs in endothelial, neuronal, and glial cells: modulation by interleukin-1. Brain Res. 16: 128– 134.

70. Foudraine, N. A.,, R. M. Hoetelmans,, J. M. Lange,, F. de Wolf,, B. H. van Benthem,, J. J. Maas,, I. P. Keet, and, P. Portegies. 1998. Cerebrospinal-fluid HIV-1 RNA and drug concentrations after treatment with lamivudine plus zidovudine or stavudine. Lancet 351: 1547– 1551.

71. Gaines, H.,, M. von Sydow,, P. O. Pehrson, and, P. Lundbergh. 1988. Clinical picture of primary HIV-1 infection presenting as a glandular-fever-like illness. Lancet 297: 1363– 1368.

72. Gartner, S. 2000. HIV infection and dementia. Science 287: 602– 604.

73. Gelman, B. B. 1993. Diffuse microgliosis associated with cerebral atrophy in the acquired immunodeficiency syndrome. Ann. Neurol. 34: 65– 70.

74. Gelman, B. B.,, and F. C. Guinto. 1992. Morphometry, histo-pathology and tomography of cerebral atrophy in the acquired immunodeficiency syndrome. Ann. Neurol. 32: 31– 40.

75. Gelman, B. B.,, V. M. Soukup,, K. W. Schuenke,, M. J. Keherly,, C. Holzer III,, F. J. Richey, and, C. J. Lahart. 2004. Acquired neuronal channelopathies in HIV-associated dementia. Neuroimmunology 157: 111– 119.

76. Giometto, B.,, S. F. An,, M. Groves,, T. Scaravilli,, J. F. Geddes,, R. Miller,, B. Tavolato,, A. A. Beckett, and, F. Scaravilli. 1997. Accumulation of β amyloid precursor protein in HIV encephalitis: relationship with neuropsychological abnormalities. Ann. Neurol. 42: 34– 40.

77. Gisslen, M.,, G. Norkrans,, B. Svennerholm, and, L. Hagberg. 1997. The effect on human immunodeficiency virus type 1 RNA levels in the cerebrospinal fluid after initiation of zidovudine or didanosine. J. Infect. Dis. 175: 434– 437.

78. Glass, J. D.,, S. L. Wesselingh,, O. A. Selnes, and, J. C. McArthur. 1993. Clinical-neuropathologic correlation in HIV-associated dementia. Neurology 43: 2230– 2237.

79. Gonzalez, E.,, B. H. Rovin,, L. Sen,, G. Cooke,, R. Dhanda,, S. Mummidi,, H. Kulkarni,, M. J. Bamshad,, V. Telles,, S. A. Anderson,, E. A. Walter,, K. T. Stephan,, M. Deucher,, A. Mangano,, R. Bologna,, S. S. Ahuja,, M. J. Dolan, and, S. K. Ahuja. 2002. HIV-1 infection and AIDS dementia are influenced by a mutant MCP-1 allele linked to increased monocyte infiltration of tissues and MCP-1 levels. Proc. Natl. Acad. Sci. USA 99: 13795– 13800.

80. Gray, F.,, H. Adle-Biassette,, F. Chretien,, G. Lorin de la Grandmaison,, G. Force, and, C. Keohane. 2001. Neuropathology and neurodegeneration in human immunodeficiency virus infection. Pathogenesis of HIV-induced lesions of the brain, correlations with HIV-associated disorders and modifications according to treatments. Clin. Neuropathol. 20: 146– 155.

81. Gray, F.,, F. Chretien,, A. V. Vallat-Decouvelaere, and, F. Scaravilli. 2003. The changing pattern of HIV neuropathology in the HAART era. J. Neuropathol. Exp. Neurol. 62: 429– 440.

82. Hagberg, L.,, B.-E. Malmvall,, L. Svennerholm,, K. Alestig, and, G. Norkrans. 1986. Guillain-Barre syndrome as an early manifestation of HIV-1 central nervous system infection. Scand. J. Infect. Dis. 18: 591– 592.

83. Hardy, W. D.,, E. S. Daar,, R. T. Sokolov, Jr., and, D. D. Ho. 1991. Acute neurologic deterioration in a young man. Rev. Infect. Dis. 13: 745– 750.

84. Harrison, L. H.,, and M. Schechter. 1998. Coinfection with HTLV-I and HIV: increase in HTLV-I-related outcomes but not accelerated HIV disease progression ? AIDS Patient Care STDs 12: 619– 623.

85. Harrison, L. H.,, B. Vaz,, D. M. Taveira,, T. C. Quinn,, C. J. Gibbs,, S. H. de Souza,, J. C. McArthur, and, M. Schechter. 1997. Myelopathy among Brazilians coinfected with human T-cell lymphotropic virus type I and HIV. Neurology 48: 13– 18.

86. Herzberg, U.,, and J. Sagen. 2001. Peripheral nerve exposure to HIV viral envelope protein gp120 induces neuropathic pain and spinal gliosis. J. Neuroimmunol. 116: 29– 39.

87. Heyes, M. P.,, B. J. Brew,, A. Martin,, R. W. Price,, A. M. Salazar,, J. J. Sidtis,, J. A. Yergey,, M. M. Mouradian,, A. E. Sadler, and, J. Keilp. 1991. Cerebrospinal fluid quinolinic acid concentrations are increased in acquired immune deficiency syndrome. Ann. Neurol. 29: 202– 209.

88. Ho, D. D.,, T. R. Rota,, R. T. Schooley,, J. C. Kaplan,, J. D. Allan,, J. E. Groopman,, L. Resnick,, D. Felsenstein,, C. A. Andrews, and, M. S. Hirsch. 1985a. Isolation of HTLV-III from cerebrospinal fluid and neural tissues of patients with neurologic syndromes related to the acquired immunodeficiency syndrome. N. Engl. J. Med. 313: 1493– 1497.

89. Ho, D. D.,, M. G. Sarngadharan,, L. Resnick,, F. Dimarzo-Veronese,, T. R. Rota, and, M. S. Hirsch. 1985b. Primary human T-lymphotropic virus type III infection. Ann. Intern. Med. 103: 880– 883.

90. Hollander, H.,, and S. Stringari. 1987. Human immunodeficiency virus-associated meningitis. Clinical course and correlations. Am. J. Med. 83: 813– 816.

91. Jarvik, J. G.,, J. R. Hesselink,, C. Kennedy,, R. Teschke,, C. Wiley,, S. Spector,, D. Richman, and, J. A. McCutchan. 1988. Acquired immunodeficiency syndrome. Magnetic resonance patterns of brain involvement with pathologic correlation. Arch. Neurol. 45: 731– 736.

92. Kahn, J. O.,, and B. D. Walker. 1998. Acute human immunodeficiency virus type 1 infection. N. Engl. J. Med. 339: 33– 39.

93. Kassutto, S.,, and E. S. Rosenberg. 2004. Primary HIV type 1 infection. Clin. Infect. Dis. 38: 1447– 1453.

94. Kaufman, D. E.,, M. Lichterfeld,, M. Altfield,, M. M. Addo,, M. N. Johnston,, P. K. Lee,, B. S. Wagner,, E. T. Kalife,, D. Strick,, E. S. Rosenberg, and, B. D. Walker. 2004. Limited durability of viral control following treated acute HIV infection. PLoS Med. 1: 1– 12.

95. Kaufman, G.,, C. Duncombe,, J. Zaunders,, P. Cunningham, and, D. Cooper. 1998. Primary HIV-1 infection: a review of clinical manifestations, immunologic and virologic changes. AIDS Patient Care STDs 12: 759– 767.

96. Keswani, S. C.,, G. J. Leitz, and, A. Hoke. 2004. Erythropoietin is neuroprotective in models of HIV sensory neuropathy. Neurosci. Lett. 371: 102– 105.

97. Keswani, S. C.,, M. Polley,, C. A. Pardo,, J. W. Griffin,, J. C. McArthur, and, A. Hoke. 2003. Schwann cell chemokine receptors mediate HIV-1 gp120 toxicity to sensory neurons. Ann. Neurol. 54: 287– 296.

98. Kieburtz, K.,, D. Simpson,, C. Yiannoutsos,, M. B. Max,, C. D. Hall,, R. J. Ellis,, C. M. Marra,, R. McKendall,, E. Singer,, G. J. Dal Pan,, D. B. Clifford,, T. Tucker,, B. Cohen, et al. 1998. A randomized trial of amitriptyline and mexiletine for painful neuropathy in HIV infection. Neurology 51: 1682– 1688.

99. Kim, R. B.,, M. F. Fromm,, C. Wandel,, B. Leake,, A. J. Wood,, D. M. Roden, and, G. R. Wilkinson. 1998. The drug transporter P glycoprotein limits oral absorption and brain entry of the HIV-1 protease inhibitors. J. Clin. Investig. 101: 289– 294.

100. Kinloch-de Loes, S.,, and T. V. Perneger. 1997. Primary HIV infection: follow up of patients initially randomized to zidovudine or placebo. J. Infect. 333: 408– 413.

101. Kivipelto, M.,, E. L. Helkala,, M. P. Laakso,, T. Hanninen,, M. Hallikainen,, K. Alhainen,, S. Iivonen,, A. Mannermaa,, J. Tuomilehto,, A. Nissinen, and, H. Soininen. 2002. Apolipoprotein E epsilon4 allele, elevated midlife total cholesterol level, and high midlife systolic blood pressure are independent risk factors for late-life Alzheimer disease. Ann. Intern. Med. 137: 149– 155.

102. Konig, J.,, A. T. Nies,, Y. Cui,, I. Leier, and, D. Keppler. 1999. Conjugate export pumps of the multidrug resistance protein (MRP) family: localization, substrate specificity, and MRP2-mediated drug resistance. Biochim. Biophys. Acta 1461: 377– 394.

103. Krathwohl, M. D.,, and J. L. Kaiser. 2004. HIV-1 promotes quiescence in human neural progenitor cells. J. Infect. Dis. 190: 216– 226.

104. Langford, D.,, A. Grigorian,, R. Hurford,, A. Adame,, R. J. Ellis,, L. Hansen, and, E. Masliah. 2004. Altered P-glycoprotein expression in AIDS patients with HIV encephalitis. J. Neuropathol. Exp. Neurol. 63: 1038– 1047.

105. Lanjewar, D. N.,, P. P. Jain, and, C. R. Shetty. 1998. Profile of central nervous system pathology in patients with AIDS: an autopsy study from India. AIDS 12: 309– 313.

106. Levy, R. M.,, D. E. Bredesen, and, M. L. Rosenblum. 1985. Neurological manifestations of the acquired immunodeficiency syndrome (AIDS): experience at UCSF and review of the literature. J. Neurosurg. 62: 475– 495.

107. Lichtenstein, K. A.,, C. Armon,, A. Baron,, A. C. Moorman,, K. C. Wood,, S. D. Holmberg, and the HIV Outpatient Study Investigators. 2005. Modification of the incidence of drug-associated symmetrical peripheral neuropathy by host and disease factors in the HIV outpatient study cohort. Clin. Infect. Dis. 40: 148– 157.

108. Lipton, S. A.,, and H. E. Gendelman. 1995. Dementia associated with the Acquired Immunodeficiency Syndrome. N. Engl. J. Med. 332: 934– 940.

109. Lori, F.,, A. Malykh,, A. Cara,, D. Sun,, J. N. Weinstein,, J. Lisziewicz, and, R. C. Gallo. 1994. Hydroxyurea as an inhibitor of human immunodeficiency virus type 1 replication. Science 266: 801– 805.

110. Markus, R.,, and B. J. Brew. 1998. HIV-1 peripheral neuropathy and combination antiretroviral therapy. Lancet 352: 1906– 1907.

111. Marshall, D. W.,, R. L. Brey,, W. T. Cahill,, R. W. Houk,, R. A. Zajac, and, R. N. Boswell. 1988. Spectrum of cerebrospinal fluid findings in various stages of human immunodeficiency virus infection. Arch. Neurol. 45: 954– 958.

112. Martin, C.,, G. Solders,, A. Sönnerborg, and, P. Hansson. 2000. Antiretroviral therapy may improve sensory function in HIV-infected patients: a pilot study. Neurology 54: 2120– 2127.

113. Martin, C.,, A. Sonnerborg,, J. O. Svensson, and, L. Stahle. 1999. Indinavir-based treatment of HIV-1 infected patients: efficacy in the central nervous system. AIDS 13: 1227– 1232.

114. Martin, J. L.,, C. E. Brown,, N. Matthews-Davis, and, J. E. Reardon. 1994. Effects of antiviral nucleoside analogs on human DNA polymerases and mitochondrial DNA synthesis. Antimicrob. Agents Chemother. 38: 2743– 2749.

115. Maruff, P.,, J. Currie,, V. Malone,, C. McArthur-Jackson,, B. Mulhall, and, E. Benson. 1994. Neuropsychological characterisation of the AIDS dementia complex and rationalisation of a test battery. Arch. Neurol. 51: 689– 695.

116. Maschke, M.,, O. Kastrup,, S. Esser,, B. Ross,, U. Hengge, and, A. Hufnagel. 2000. Incidence and prevalence of HIV-associated neurological disorders since the introduction of highly active antiretroviral therapy (HAART). J. Neurol. Neurosurg. Psychiatry 69: 376– 380.

117. Masliah, E.,, R. K. Heaton,, T. D. Marcotte,, R. J. Ellis,, C. A. Wiley,, M. Mallory,, C. L. Achim,, J. A. McCutchan,, J. A. Nelson,, J. H. Atkinson, and, I. Grant. 1997. Dendritic injury is a pathological substrate for human immunodeficiency virus related cognitive disorders. Ann. Neurol. 42: 963– 972.

118. McArthur, J. C.,, and J. W. Griffin. 2005. Another tool for the neurologist’s toolbox. Ann. Neurol. 57: 163– 167.

119. McArthur, J. C.,, D. R. Hoover,, H. Bacellar,, E. N. Miller,, B. A. Cohen,, J. T. Becker,, N. M. Graham,, J. H. McArthur,, O. A. Selnes, and, L. P. Jacobson. 1993. Dementia in AIDS patients: incidence and risk factors. Multicenter AIDS Cohort Study. Neurology 43: 2245– 2252.

120. McArthur, J. C.,, D. R. McClernon,, M. F. Cronin,, T. E. Nance-Sproson,, A. J. Saah,, M. St Clair, and, E. R. Lanier. 1997. Relationship between human immunodeficiency virus-associated dementia and viral load in cerebrospinal fluid and brain. Ann. Neurol. 42: 689– 698.

121. McArthur, J. C.,, M. P. McDermott,, D. McClernon,, C. St Hillaire,, K. Conant,, K. Marder,, G. Schifitto,, O. A. Selnes,, N. Sacktor,, Y. Stern,, S. M. Albert,, K. Kieburtz,, J. A. deMarcaida,, B. Cohen, and, L. G. Epstein. 2004. Attenuated central nervous system infection in advanced HIV/AIDS with combination antiretroviral therapy. Arch. Neurol. 61: 1687– 1696.

122. McArthur, J. C.,, C. Yiannoutsos,, D. M. Simpson,, B. T. Adornato,, E. J. Singer,, H. Hollander,, C. Marra,, M. Rubin,, B. A. Cohen,, T. Tucker,, B. A. Navia,, G. Schifitto,, D. Katzenstein,, C. Rask,, L. Zaborski,, M. E. Smith,, S. Shrivers,, L. Millar,, D. B. Clifford,, I. J. Karalnik, et al. 2000. A phase II trial of nerve growth factor for sensory neuropathy associated with HIV infection. Neurology 54: 1080– 1088.

123. McDonagh, C. A.,, and R. P. Holman. 2003. Primary human immunodeficiency virus type 1 infection in a patient with acute rhabdomyolysis. South. Med. J. 96: 1027– 1030.

124. Mizuno, T.,, J. Kawanokuchi,, K. Numata, and, A. Suzumura. 2003. Production and neuroprotective functions of fractalkine in the central nervous system. Brain Res. 979: 65– 70.

125. Monos, D. S.,, M. Papaioakim,, T. W. Ho,, C. Y. Li, and, G. M. McKhann. 1997. Differential distribution of HLA alleles in two forms of Guillain-Barre syndrome. J. Infect. Dis. 176 (Suppl. 2) : S180– S182.

126. Morgello, S.,, R. Mahboob,, T. Yakoushina,, S. Khan, and, K. Hague. 2002. Autopsy findings in a human immunodeficiency virus-infected population over 2 decades: influences of gender, ethnicity, risk factors, and time. Arch. Pathol. Lab. Med. 126: 182– 190.

127. Moses, A. E.,, K. A. Adelowo, and, E. A. Nwankwo. 2001. Effect of HIV infection on the clinical spectrum of leprosy in Maiduguri. Niger. Postgrad. Med. J. 8: 74– 77.

128. Moses, A. V.,, S. G. Stenglein, and, J. A. Nelson. 1996. HIV infection of the brain microvasculature and its contribution to the AIDS dementia complex. J. NeuroAIDS 1: 85– 100.

129. Moulignier, A.,, F. J. Authier,, M. Baudrimont,, G. Pialoux,, L. Belec,, M. Polivka,, B. Clair,, F. Gray,, J. Mikol, and, R. K. Gherardi. 1997. Peripheral neuropathy in human immunodeficiency virus-infected patients with the diffuse infiltrative lymphocytosis syndrome. Ann. Neurol. 41: 438– 445.

130. Navia, B. A.,, B. D. Jordan, and, R. W. Price. 1986. The AIDS dementia complex. I. Clinical features. Ann. Neurol. 19: 517– 524.

131. Nebuloni, M.,, A. Pellegrinelli,, A. Ferri,, S. Bonetto,, R. Boldorini,, L. Vago,, M. P. Grassi, and, G. Costanzi. 2001. Beta amyloid precursor protein and patterns of HIV p24 immunohistochemistry in different brain areas of AIDS patients. AIDS 15: 571– 575.

132. Pardo, C. A.,, J. C. McArthur, and, J. W. Griffin. 2001. HIV neuropathy: insights in the pathology of HIV peripheral nerve disease. J. Peripher. Nerv. Syst. 6: 21– 27.

133. Paton, P.,, H. Poly,, P.-M. Gonnaud,, J. C. Tardy,, J. Fontana,, K. Kindbeiter,, R. Tete, and, J. J. Madjar. 1990. Acute meningoradiculitis concomitant with seroconversion to human immunodeficiency virus type 1. Res. Virol. 141: 427– 433.

134. Pedersen, C.,, B. Lindhardt,, B. L. Jensen,, E. Lauritzen,, J. Gerstoft,, E. Dickmeiss,, J. Gaub,, E. Scheibel, and, T. Karlsmark. 1989. Clinical course of primary HIV-1 infection: consequences for subsequent course of infection. Br. Med. J. 299: 154– 157.

135. Petito, C. K.,, B. A. Navia,, E. S. Cho,, B. D. Jordan,, D. C. George, and, R. W. Price. 1985. Vacuolar myelopathy pathologically resembling subacute combined degeneration in patients with acquired immunodeficiency syndrome. N. Engl. J. Med. 312: 874– 879.

136. Piette, A. M.,, F. Tusseau,, D. Vignon,, A. Chapman,, G. Parrot,, J. Leibowitch, and, L. Montagnier. 1986. Acute neuropathy coincident with seroconversion for anti-LAV/HTLV-III. Lancet i: 852.

137. Piller, S. C.,, G. D. Ewart,, D. A. Jans,, P. W. Gage, and, G. B. Cox. 1999. The amino-terminal region of Vpr from human immunodeficiency virus type 1 forms ion channels and kills neurons. J. Virol. 73: 4230– 4238.

138. Portegies, P.,, R. H. Enting,, J. de Gans,, P. R. Algra,, M. M. Derix,, J. M. Lange, and, J. Goudsmit. 1993. Presentation and course of AIDS dementia complex: 10 years of follow-up in Amsterdam, The Netherlands. AIDS 7: 669– 775.

139. Power, C.,, P. A. Kong,, T. O. Crawford,, S. Wesselingh,, J. D. Glass,, J. C. McArthur, and, B. D. Trapp. 1993. Cerebral white matter changes in acquired immunodeficiency syndrome dementia: alterations of the blood brain barrier. Ann. Neurol. 34: 339– 359.

140. Quasney, M. W.,, Q. Zhang,, S. Sargent,, M. Mynatt,, J. Glass, and, J. McArthur. 2001. Increased frequency of the tumor necrosis factor-alpha-308 A allele in adults with human immunodeficiency virus dementia. Ann. Neurol. 50: 157– 162.

141. Quinn, T. C. 1997. Acute primary HIV infection. JAMA 278: 58– 62.

142. Radja, F.,, D. G. Kay,, S. Albrecht, and, P. Jolicoeur. 2003. Oligodendrocyte-specific expression of human immunodeficiency virus type 1 Nef in transgenic mice leads to vacuolar myelopathy and alters oligodendrocyte phenotype in vitro. J. Virol. 77: 11745– 11753.

143. Ragin, A. B.,, P. Storey,, B. A. Cohen,, R. R. Edelman, and, L. G. Epstein. 2004. Disease burden in HIV-associated cognitive impairment: a study of whole-brain imaging measures. Neurology 63: 2293– 2297.

144. Ranga, U.,, R. Shankarappa,, N. B. Siddappa,, L. Ramakrishna,, R. Nagendran,, M. Mahalingam,, A. Mahadevan,, N. Jayasuryan,, P. Satishchandra,, S. K. Shankar, and, V. R. Prasad. 2004. Tat protein of human immunodeficiency virus type 1 subtype C strains is a defective chemokine. J. Virol. 78: 2586– 2590.

145. Rempel, H. C.,, and L. Pulliam. 2005. HIV-1 Tat inhibits neprilysin and elevates amyloid beta. AIDS 19: 127– 135.

146. Rizzardi, G. P.,, A. Harari,, B. Capiluppi,, G. Tambussi,, K. Ellefsen,, D. Ciuffreda,, P. Champagne,, P. A. Bart,, J. P. Chave,, A. Lazzarin, and, G. Pantaleo. 2002. Treatment of primary HIV-1 infection with cyclosporine A coupled with highly active antiretroviral therapy. J. Clin. Investig. 109: 681– 688.

147. Romanelli, F.,, H. R. Jennings,, A. Nath,, M. Ryan, and, J. Berger. 2000. Therapeutic dilemma: the use of anticonvulsants in HIV-positive individuals. Neurology 54: 1404– 1407.

148. Rosenblum, M.,, A. C. Scheck,, K. Cronin,, B. J. Brew,, A. Khan,, M. Paul, and, R. W. Price. 1989. Dissociation of AIDS related vacuolar myelopathy and productive HIV-1 infection of the spinal cord. Neurology 39: 892– 896.

149. Rottenberg, D. A.,, J. R. Moeller,, S. C. Strother,, J. J. Sidtis,, B. A. Navia,, V. Dhawan,, J. Z. Ginos, and, R. W. Price. 1987. The metabolic pathology of the AIDS dementia complex. Ann. Neurol. 22: 700– 706.

150. Rottnek, M.,, A. Di Rocco,, D. Laudier, and, S. Morgello. 2002. Axonal damage is a late component of vacuolar myelopathy. Neurology 58: 479– 481.

151. Roucoux, D. F.,, and E. L. Murphy. 2004. The epidemiology and disease outcomes of human T-lymphotropic virus type II. AIDS Rev. 6: 144– 154.

152. Ryan, E. L.,, S. Morgello,, K. Isaacs,, M. Naseer, and, P. Gerits. 2004. Neuropsychiatric impact of hepatitis C on advanced HIV. Neurology 62: 957– 962.

153. Saavedra-Lozano, J.,, C. C. McCoig,, Y. Cao,, E. S. Vitetta, and, O. Ramilo. 2004. Zidovudine, lamivudine, and abacavir have different effects on resting cells infected with human immunodeficiency virus in vitro. Antimicrob. Agents Chemother. 48: 2825– 2830.

154. Sanders, V. J.,, C. A. Pittman,, M. G. White,, G. Wang,, C. A. Wiley, and, C. L. Achim. 1998. Chemokines and receptors in HIV encephalitis. AIDS 12: 1021– 1026.

155. Schacker, T.,, A. C. Collier,, J. Hughes,, T. Shea, and, L. Corey. 1996. Clinical and epidemiologic features of primary HIV infection. Ann. Intern. Med. 125: 257– 264.

156. Schielke, E.,, K. Tatsch,, H. W. Pfister,, C. Trenkwalder,, G. Leinsinger,, C. M. Kirsch,, A. Matuschke, and, K. M. Einhaupl. 1990. Reduced cerebral blood flow in early stages of human immunodeficiency virus infection. Arch. Neurol. 47: 1342– 1345.

157. Schifitto, G.,, M. P. McDermott,, J. C. McArthur,, K. Marder,, N. Sacktor,, D. R. McClernon,, K. Conant,, B. Cohen,, L. G. Epstein,, K. Kieburtz, and the NEAD Consortium. 2005. Markers of immune activation and viral load in HIV-associated sensory neuropathy. Neurology 64: 842– 848.

158. Schutzer, S. E.,, M. Brunner,, H. M. Fillit, and, J. R. Berger. 2003. Autoimmune markers in HIV-associated dementia. J. Neuroimmunol. 138: 156– 161.

159. Si, Q.,, M. Cosenza,, M. O. Kim,, M. L. Zhao,, M. Brownlee,, H. Goldstein, and, S. Lee. 2004. A novel action of minocycline: inhibition of human immunodeficiency virus type 1 infection in microglia. J. Neurovirol. 10: 284– 292.

160. Sidtis, J. J.,, C. Gatsonis,, R. W. Price,, E. J. Singer,, A. C. Collier,, D. D. Richman,, M. S. Hirsch,, F. W. Schaerf,, M. A. Fischl,, K. Kieburtz, et al. 1993. Zidovudine treatment of the AIDS dementia complex: results of a placebo controlled trial. Ann. Neurol. 33: 343– 349.

161. Silver, B.,, K. McAvoy,, S. Mikesell, and, T. W. Smith. 1997. Fulminating encephalopathy with perivenular demyelination and vacuolar myelopathy as the initial presentation of human immunodeficiency virus infection. Arch. Neurol. 54: 647– 650.

162. Simpson, D. M.,, J. C. McArthur,, R. Olney,, D. Clifford,, Y. So,, D. Ross,, B. J. Baird,, P. Barrett,, A. E. Hammer, and the Lamotrigine HIV Neuropathy Study Team. 2003. Lamotrigine for HIV-associated painful sensory neuropathies: a placebo-controlled trial. Neurology 60: 1508– 1514.

163. Sinclair, E.,, F. Gray,, A. Giardi, and, F. Scaravilli. 1994. Immunohistochemical changes and PCR detection of HIV provirus DNA in brains of asymptomatic HIV positive patients. J. Neuropathol. Exp. Neurol. 53: 43– 50.

164. Singh, K. K.,, C. F. Barroga,, M. D. Hughes,, J. Chen,, C. Raskino,, R. E. McKinney, and, S. A. Spector. 2003. Genetic influence of CCR5, CCR2, and SDF1 variants on human immunodeficiency virus 1 (HIV-1)-related disease progression and neurological impairment, in children with symptomatic HIV-1 infection. J. Infect. Dis. 188: 1461– 1472.

165. Smit, T. K.,, B. J. Brew,, W. Tourtellotte,, S. Morgello,, B. B. Gelman, and, N. K. Saksena. 2004. 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. 78: 10133– 10148.

166. Smith, D. E.,, B. D. Walker,, D. A. Cooper,, E. S. Rosenberg, and, J. M. Kaldor. 2004. Is antiretroviral treatment of primary HIV infection clinically justified on the basis of current evidence ? AIDS 18: 709– 718.

167. Stanley, L. C.,, R. E. Mrak,, R. C. Woody,, L. J. Perrot,, S. Zhang,, D. R. Marshak,, S. J. Nelson, and, W. S. Griffin. 1994. Glial cytokines as neuropathogenic factors in HIV infection: pathogenic similarities to Alzheimer’s disease. J. Neuropathol. Exp. Neurol. 53: 231– 238.

168. Steiner, I.,, O. Cohen,, R. R. Leker,, B. Rubinovitch,, R. Handsher,, S. Hassin-Baer,, D. H. Gilden, and, M. Sadeh. 1999. Subacute painful lumbosacral polyradiculoneuropathy in immunocompromised patients. J. Neurol. Sci. 162: 91– 93.

169. Takahashi, K.,, S. L. Wesselingh,, D. E. Griffin,, J. C. McArthur,, R. T. Johnson, and, J. D. Glass. 1996. Localization of HIV-1 in human brain using polymerase chain reaction/in situ hybridization and immunohistochemistry. Ann. Neurol. 39: 705– 711.

170. Tambussi, G.,, A. Gori,, B. Capiluppi,, C. Balotta,, L. Papagno,, B. Morandini,, M. Di Pietro,, D. Ciuffreda,, A. Saracco, and, A. Lazzarin. 2000. Neurological symptoms during primary human immunodeficiency virus (HIV) infection correlate with high levels of HIV RNA in cerebrospinal fluid. Clin. Infect. Dis. 30: 962– 965.

171. Thompson, K. A.,, J. C. McArthur, and, S. L. Wesselingh. 2001. Correlation between neurological progression and astrocyte apoptosis in HIV-associated dementia. Ann. Neurol. 49: 745– 752.

172. Tornatore, C.,, R. Chandra,, J. R. Berger, and, E. O. Major. 1994. HIV-1 infection of subcortical astrocytes in the pediatric central nervous system. Neurology 44: 481– 487.

173. Tyor, W. R.,, J. D. Glass,, J. W. Griffin,, P. S. Becker,, J. C. McArthur,, L. Bezman, and, D. E. Griffin. 1992. Cytokine expression in the brain during the acquired immune deficiency syndrome. Ann. Neurol. 31: 349– 360.

174. Waxman, S. G. 1999. The molecular pathophysiology of pain: abnormal expression of sodium channel genes and its contributions to hyperexcitability of primary sensory neurons. Pain 1999 (Suppl. 6) : S133– S140.

175. Weidenheim, K. M.,, M. Ausubel, and, W. D. Lyman. 1996. Quantification of microglia in vacuolar myelopathy is a more sensitive measure of pathology than changes in myelin protein immunoreactivity. J. Neuropathol. Exp. Neurol. 55: 660.

176. Wesselingh, S. L.,, C. Power,, J. D. Glass,, W. R. Tyor,, J. C. McArthur,, J. M. Farber,, J. W. Griffin, and, D. E. Griffin. 1993. Intracerebral cytokine messenger RNA expression in acquired immunodeficiency syndrome dementia. Ann. Neurol. 33: 576– 582.

177. Whiteman, M.,, L. Espinoza,, M. J. Post,, M. D. Bell, and, S. Falcone. 1995. Central nervous system tuberculosis in HIV-infected patients: clinical and radiographic findings. Am. J. Neuroradiol. 16: 1319– 1327.

178. Wilkins, J. W.,, K. R. Robertson,, C. R. Snyder,, W. K. Robertson,, C. van der Horst, and, C. D. Hall. 1991. Implications of self reported cognitive and motor dysfunction in HIV positive patients. Am. J. Psychiatry 148: 641– 643.

179. Wiselka, M. J.,, K. G. Nicholson,, S. C. Ward, and, A. J. E. Flower. 1987. Acute infection with human immunodeficiency virus associated with facial nerve palsy and neuralgia. J. Infect. 15: 189– 194.

180. Wu, H. S.,, T. C. Liu,, Z. L. Lu,, L. P. Zou,, W. C. Zhang,, G. Zhaori, and, J. Zhang. 1997. A prospective clinical and electrophysiologic survey of acute flaccid paralysis in Chinese children. Neurology 49: 1723– 1725.

181. Zeman, A.,, and M. Donaghy. 1991. Acute infection with human immunodeficiency virus presenting with neurogenic urinary retention. Genitourin. Med. 67: 345– 347.

182. Zhang, K.,, G. A. McQuibban,, C. Silva,, G. S. Butler,, J. B. Johnston,, J. Holden,, I. Clark-Lewis,, C. M. Overall, and, C. Power. 2003. HIV-induced metalloproteinase processing of the chemokine stromal cell derived factor-1 causes neurodegeneration. Nat. Neurosci. 6: 1064– 1071.

183. Zink, M. C.,, and J. E. Clements. 2002. A novel simian immunodeficiency virus model that provides insight into mechanisms of human immunodeficiency virus central nervous system disease. J. Neurovirol. 8 (Suppl. 2) : S42– S48.

Tables

Global Issues in Neuro-AIDS and Their Evolution over the Future of the HAART Era

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/content/10.1128/9781555815691.ch36.ch36tab01

TABLE 1

A preliminary classification of ADC

TABLE 1

A preliminary classification of ADC

/content/10.1128/9781555815691.ch36.ch36tab02

TABLE 2

Investigations for the diagnosis of ADC

TABLE 2

Investigations for the diagnosis of ADC