Skip to main content Accessibility help
Hostname: page-component-544b6db54f-mdtzd Total loading time: 0.527 Render date: 2021-10-22T12:11:07.880Z Has data issue: true Feature Flags: { "shouldUseShareProductTool": true, "shouldUseHypothesis": true, "isUnsiloEnabled": true, "metricsAbstractViews": false, "figures": true, "newCiteModal": false, "newCitedByModal": true, "newEcommerce": true, "newUsageEvents": true }

Progress in Clinical Neurosciences: The Neuropathogenesis of HIV Infection: Host-Virus Interaction and the Impact of Therapy

Published online by Cambridge University Press:  02 December 2014

C. Power
Departments of Clinical Neurosciences, University of Calgary, Calgary AB, Canada
M.J. Gill
Medicine University of Calgary, Calgary AB, Canada
R.T. Johnson
Department of Neurology, Johns Hopkins University, Baltimore MD, USA.
Rights & Permissions[Opens in a new window]


HTML view is not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Despite the availability of highly active antiretroviral therapy (HAART), primary HIV-related neurological diseases remain major problems in HIV clinics. The present review examines the pathogenesis of HIV-related dementia and the less severe minor cognitive and motor deficit, together with distal sensory and drug-induced toxic polyneuropathies. Abnormal host immune responses within the nervous system and the role of viral expression and diversity are emphasized in relation to neurovirulence. Induction of innate immune responses within the central and peripheral nervous systems, largely mediated by cells of macrophage lineage, appear to be common to the development of primary HIV-related neurological disease. Activation of these cell types results in the release of a cascade of inflammatory molecules including cytokines, chemokines, matrix metalloproteinases, and arachidonic acid metabolites that influence neuronal survival. Individual viral proteins encoded by envelope and tat genes and discrete sequences within these genes influence the extent to which these pro-inflammatory molecules are induced. At the same time, systemic immune suppression may influence the occurrence and severity of HIV-related neurological diseases. Implementation of HAART and neuroprotective treatments improves neurological function although the evolution of drug-resistant viral strains limits the sustained benefits of HAART.



Malgré la disponibilité de la thérapie antirétrovirale hautement efficace (HAART), les maladies neurologiques reliées à l'infection par le VIH demeurent un problème majeur dans les cliniques de traitement de l'infection par le VIH. Cette revue examine la pathogenèse de la démence reliée au VIH et des déficits cognitifs et moteurs de moindre importance, ainsi que les polyneuropathies sensitives distales, induites par la toxicité des médicaments. Les réponses immunitaires anormales de l'hôte dans le système nerveux et le rôle de l'expression et de la diversité virale sont soulignés en relation avec la neurovirulence. L'induction des réponses immunitaires innées dans le système nerveux central et périphérique, en grande partie médiée par les cellules de la lignée macrophagique, semble être commune au développement des maladies neurologiques reliées au VIH. L'activation de ces types de cellules provoque la libération d'une cascade de molécules inflammatoires incluant des cytokines, des chemokines, des métalloprotéinases de la matrice et des métabolites de l'acide arachidonique qui influencent la survie neuronale. Des protéines virales individuelles codées par des gènes de l'enveloppe et des gènes tat, ainsi que des séquences discrètes dans ces gènes, influencent le niveau d'induction de ces molécules pro-inflammatoires. De plus, la suppression immunitaire systémique peut influencer l'apparition et la sévérité de maladies neurologiques reliées au VIH. Le traitement HAART et les traitements neuroprotecteurs améliorent la fonction neurologique, bien que l'évolution de souches virales résistantes à la médication limite les bénéfices à long terme du traitement HAART.

Review Article
Copyright © Canadian Neurological Sciences Federation 2002


1. Nicoll, A, Gill, ON. The global impact of HIV infection and disease. Commun Dis Public Health 1999;2:8595.Google ScholarPubMed
2. Johnson, R. Viral Infections of the Nervous System. 2nd Ed. Philadelphia: Lippincott-Raven Publishers, 1998.Google Scholar
3. Power, C, Johnson, RT. HIV-1 associated dementia: clinical featuresand pathogenesis. Can J Neurol Sci 1995;22:92100.CrossRefGoogle ScholarPubMed
4. McArthur, JC. Neurologic manifestations of AIDS. Medicine(Baltimore) 1987;66:407437.Google Scholar
5. McArthur, JC, Hoover, DR, Bacellar, H, et al. Dementia in AIDSpatients: incidence and risk factors. Multicenter AIDS CohortStudy. Neurology 1993;43:22452252.CrossRefGoogle Scholar
6. White, DA, Heaton, RK, Monsch, AU. Neuropsychological studiesof asymptomatic human immunodeficiency virus- type-1 infected individuals. The HNRC Group. HIV Neurobehavioral Research Center. J Int Neuropsychol Soc 1995;1:304315.CrossRefGoogle Scholar
7. Janssen, R. Nomenclature and research case definitions forneurologic manifestations of human immunodeficiency virustype 1 (HIV-1) infection. Report of a Working Group of the American Academy of Neurology AIDS Task Force. Neurology 1991;41:778785.Google Scholar
8. Navia, BA, Jordan, BD, Price, RW. The AIDS dementia complex: I.Clinical features. Ann Neurol 1986;19:517524.CrossRefGoogle ScholarPubMed
9. Mirsattari, SM, Power, C, Nath, A. Parkinsonism with HIV infection. Mov Disord 1998;13:684689.CrossRefGoogle ScholarPubMed
10. Maher, J, Choudhri, S, Halliday, W, et al. AIDS dementia complexwith generalized myoclonus. Mov Disord 1997;12:593597.CrossRefGoogle Scholar
11. Childs, EA, Lyles, RH, Selnes, OA, et al. Plasma viral load and CD4lymphocytes predict HIV-associated dementia and sensoryneuropathy. Neurology 1999;52:607613.CrossRefGoogle Scholar
12. Sacktor, N, Lyles, RH, Skolasky, R, et al. HIV-associated neurologicdisease incidence changes: Multicenter AIDS Cohort Study, 1990–1998. Neurology 2001;56:257260.CrossRefGoogle ScholarPubMed
13. A randomized, double-blind, placebo-controlled trial of deprenyland thioctic acid in human immunodeficiency virus-associated cognitive impairment. Dana Consortium on the Therapy of HIV Dementia and Related Cognitive Disorders. Neurology 1998;50:645651.CrossRefGoogle Scholar
14. Ellis, RJ, Deutsch, R, Heaton, RK, et al. Neurocognitive impairmentis an independent risk factor for death in HIV infection. San Diego HIV Neurobehavioral Research Center Group. ArchNeurol 1997;54: 416424.Google Scholar
15. Simpson, DM, Tagliati, M. Neurologic manifestations of HIV infection [published erratum appears in Ann Intern Med 1995 Feb 15;122(4):317]. Ann Intern Med 1994;121:769785.CrossRefGoogle Scholar
16. Dal Pan, GJ, McArthur, JH, Aylward, E, et al. Patterns of cerebralatrophy in HIV-1-infected individuals: results of a quantitativeMRI analysis. Neurology 1992;42:21252130.CrossRefGoogle ScholarPubMed
17. Chang, L, Ernst, T, Leonido-Yee, M, et al. Cerebral metaboliteabnormalities correlate with clinical severity of HIV-1 cognitive motor complex. Neurology 1999;52:100108.CrossRefGoogle ScholarPubMed
18. Navia, BA, Cho, ES, Petito, CK, et al. The AIDS dementia complex: II. Neuropathology. Ann Neurol 1986;19:525535.CrossRefGoogle ScholarPubMed
19. Sharer, LR. Pathology of HIV-1 infection of the central nervoussystem. A review. J Neuropathol Exp Neurol 1992; 51:311.CrossRefGoogle Scholar
20. Vinters, HA, Anders, KH. Neuropathology of AIDS. CRC Press, Inc. Boca Raton, Florida, 1990.Google Scholar
21. Glass, M, Faull, RL, Bullock, JY, et al. Loss of A1 adenosinereceptors in human temporal lobe epilepsy. Brain Res 1996;710:5668.CrossRefGoogle ScholarPubMed
22. Sharer, LR, Epstein, LG, Cho, ES, et al. Pathologic features of AIDSencephalopathy in children:evidence for LAV/HTLV-IIIinfection of brain. Hum Pathol 1986;17:271284.CrossRefGoogle ScholarPubMed
23. Petito, CK, Cash, KS. Blood-brain barrier abnormalities in theacquired immunodeficiency syndrome: immunohistochemical localization of serum proteins in postmortem brain. Ann Neurol 1992;32:658666.CrossRefGoogle ScholarPubMed
24. Power, C, Kong, PA, Crawford, TO, et al. Cerebral white matterchanges in acquired immunodeficiency syndrome dementia: alterations of the blood-brain barrier. Ann Neurol 1993;34:339350.CrossRefGoogle ScholarPubMed
25. Shi, BD, De Girolami, U, He, J; et al, Apoptosis induced by HIV-1infection of the central nervous system. J Clin Invest 1996;98:19791990.CrossRefGoogle Scholar
26. Glass, JD, Fedor, H, Wesselingh, SL, et al. Immunocytochemical quantitation of human immunodeficiency virus in the brain: correlations with dementia. Ann Neurol 1995;38:755762.CrossRefGoogle ScholarPubMed
27. Rostasy, K, Monti, L, Yiannoutsos, C, et al. NFkappaB activation, TNF-alpha expression, and apoptosis in the AIDS- Dementia-Complex. J Neurovirol 2000;6:537543.CrossRefGoogle ScholarPubMed
28. Achim, CL, Heyes, MP, Wiley, CA. Quantitation of humanimmunodeficiency virus,immune activation factors, andquinolinic acid in AIDS brains. J Clin Invest 1993;91:27692775.CrossRefGoogle Scholar
29. Everall, IP, Luthert, PJ, Lantos, PL. Neuronal loss in the frontalcortex in HIV infection. Lancet 1991;337:11191121.CrossRefGoogle ScholarPubMed
30. Masliah, E, Ge, N, Achim, CL, et al. Selective neuronal vulnerabilityin HIV encephalitis. J Neuropathol Exp Neurol 1992;51:585593.CrossRefGoogle ScholarPubMed
31. Masliah, E, Ge, N, Morey, M, et al. Cortical dendritic pathology inhuman immunodeficiency virus encephalitis. Lab Invest 1992;66:285291.Google Scholar
32. Dal Pan, GB, Berger, JR. Spinal Cord Disease in Human Immunodeficiency Virus Infection. In: Berger, J.L. RM AIDS and the Nervous System. 2nd Ed. Philadelphia: Lippincott Raven Publishers, 1997:173187.Google Scholar
33. DiRocco, L, Dalton, T, Liang, D, et al. Nonallelism for theaudiogenic seizure prone (Asp1) and the aryl hydrocarbon receptor (Ahr) loci in mice. J Neurogenet 1998;12:191203.CrossRefGoogle ScholarPubMed
34. Fuller, GN, Jacobs, JM, Guiloff, RJ. Nature and incidence of peripheral nerve syndromes in HIV infection. J Neurol Neurosurg Psychiatry 1993;56:372381.CrossRefGoogle ScholarPubMed
35. Brannagan, TM, McAlarney, T, Latov, N, Peripheral neuropathy inHIV-1 infection. In: Latov, N.W. JH; Kelly, JJ. Immunological and Infectious Diseases of the Peripheral Nerves. Cambridge:Cambridge University Press, 1998:285307.Google Scholar
36. Price, RW. Neurological complications of HIV infection. Lancet 1996; 348: 445452.CrossRefGoogle ScholarPubMed
37. Dalakas, MC, Cupler, EJ. Neuropathies in HIV infection. BaillieresClin Neurol 1996;5:199218.Google Scholar
38. McCarthy, BG, Hsieh, ST, Stocks, A, et al. Cutaneous innervation insensory neuropathies: evaluation by skin biopsy. Neurology 1995;45: 18481855.CrossRefGoogle Scholar
39. Herrmann, DN, Griffin, JW, Hauer, P, et al. Epidermal nerve fiberdensity and sural nerve morphometry in peripheral neuropathies. Neurology 1999;53:16341640.CrossRefGoogle ScholarPubMed
40. Power, C, Johnson, RT. Neurovirological and neuroimmunologicalaspects of HIV infection. Adv Virus Res 2001; 56:579624.Google Scholar
41. Greene, WC. The molecular biology of human immunodeficiencyvirus type 1 infection. N Engl J Med 1991;324:308317.Google Scholar
42. Levy, J. HIV and the Pathogenesis of AIDS. Second Ed. American Society of Microbiology. Washington. DC, 1998.Google Scholar
43. Korber, B, Foley, B, Leitner, T, et al. Human retroviruses and AIDS. A compilation and analysis of nucleic acid and amino acid sequences. Theoretical Biology and Biophysics. Group T-10. Los Alamos: Los Alamos National Library 1997.Google Scholar
44. Collman, R, Balliet, JW, Gregory, SA, et al. An infectious molecularclone of an unusual macrophage-tropic and highly cytopathic strain of human immunodeficiency virus type 1. J Virol 1992;6:75177521.Google Scholar
45. Deng, H, Liu, R, Ellmeier, W, et al. Identification of a major co-receptor for primary isolates of HIV-1. Nature 1996;381:661666.CrossRefGoogle Scholar
46. Pierson, T, McArthur, J, Siliciano, RF. Reservoirs for HIV-1:mechanisms for viral persistence in the presence of antiviral immune responses and antiretroviral therapy. Annu Rev Immunol 2000;18:665708.CrossRefGoogle ScholarPubMed
47. Koot, M, Vos, AH, Keet, RP, et al. HIV-1 biological phenotype inlong-term infected individuals evaluatedwith an MT-2cocultivation assay. AIDS 1992;6:4954.CrossRefGoogle Scholar
48. Johnson, R. Possible viral cause of multiple sclerosis. In: ViralInfections of the Nervous System. 2nd Ed. Philadelphia: Lippincott-Raven, 1998:248258.Google Scholar
49. Power, C. Retroviral diseases of the nervous system: pathogenichost response or viral gene-mediated neurovirulence? Trends Neurosci 2001;24:162169.CrossRefGoogle ScholarPubMed
50. Koyanagi, Y, Miles, S, Mitsuyasu, RT, et al. Dual infection of thecentral nervous system by AIDS viruses with distinct cellulartropisms. Science 1987;236:819822.CrossRefGoogle Scholar
51. Bell, JE, Busuttil, A, Ironside, JW, et al. Human immunodeficiencyvirus and the brain: investigation of virus load and neuropathologic changes in pre-AIDS subjects. J Infect Dis 1993;168:818824.CrossRefGoogle Scholar
52. Budka, H. Neuropathology of human immunodeficiency virusinfection. Brain Pathol 1991;1:163175.CrossRefGoogle Scholar
53. Davis, TH, Morton, CC, Miller-Cassman, R, et al. Hodgkin’s disease,lymphomatoid papulosis, and cutaneous T-cell lymphoma derived from a common T-cell clone. N Engl J Med 1992;326:11151122.CrossRefGoogle ScholarPubMed
54. Haase, AT. Pathogenesis of lentivirus infections. Nature 1986;322:130136.CrossRefGoogle ScholarPubMed
55. Falangola, MF, Hanly, A, Galvao-Castro, B, et al. HIV infection ofhuman choroid plexus: a possible mechanism of viral entry intothe CNS. J Neuropathol Exp Neurol 1995;54:497503.CrossRefGoogle Scholar
56. Chun, TW, Fauci, AS. Latent reservoirs of HIV: obstacles to theeradication of virus. Proc Natl Acad Sci USA 1999;96:1095810961.CrossRefGoogle ScholarPubMed
57. Chen, H, Wood, C, Petito, CK. Comparisons of HIV-1 viralsequences in brain, choroid plexus and spleen: Potential role of choroid plexus in the pathogenesis of HIV encephalitis. J Neurovirol 2000;6:498506.CrossRefGoogle ScholarPubMed
58. Pierson, T, Hoffman, TL, Blankson, J, et al. Characterization of chemokine receptor utilization of viruses in the latent reservoir for human immunodeficiency virus type 1. J Virol 2000;74:78247833.CrossRefGoogle ScholarPubMed
59. Cheng-Mayer, C, Weiss, C, Seto, D, et al. Isolates of humanimmunodeficiency virus type 1 from the brain may constitute a special group of the AIDS virus. Proc Natl Acad Sci USA 1989;86:85758579.CrossRefGoogle Scholar
60. Reddy, RT, Achim, CL, Sirko, DA, et al. Sequence analysis of the V3loop in brain and spleen of patients with HIV encephalitis. AIDS Res Hum Retroviruses 1996;12:477482.CrossRefGoogle ScholarPubMed
61. Power, C, McArthur, JC, Johnson, RT, et al. Demented andnondemented patients with AIDS differ in brain-derived human immunodeficiency virus type 1 envelope sequences. J Virol 1994;68:46434649.Google ScholarPubMed
62. Letendre, SL, Lanier, ER, McCutchan, JA. Cerebrospinal fluid betachemokine concentrations in neurocognitively impaired individuals infected with human immunodeficiency virus type 1. J Infect Dis 1999;180:310319.CrossRefGoogle Scholar
63. Hurwitz, AA, Berman, JW, Lyman, WD. The role of the blood-brainbarrier in HIV infection of the central nervous system. Adv Neuroimmunol 1994;4:249256.CrossRefGoogle Scholar
64. McArthur, JC, McClernon, DR, Cronin, MF, et al. Relationshipbetween human immunodeficiency virus-associated dementia and viral load in cerebrospinal fluid and brain. Ann Neurol 1997;42:689698.CrossRefGoogle Scholar
65. Brew, BJ, Pemberton, L, Cunningham, P, et al. Levels of humanimmunodeficiency virus type 1 RNA in cerebrospinal fluidcorrelate with AIDS dementia stage. J Infect Dis 1997;175:963966.CrossRefGoogle Scholar
66. Koenig, S, Gendelman, HE, Orenstein, JM, et al. Detection of AIDSvirus in macrophages in brain tissue from AIDS patients withencephalopathy. Science 1986; 233:10891093.CrossRefGoogle Scholar
67. Wiley, CA, Schrier, RD, Nelson, JA, et al. Cellular localization of human immunodeficiency virus infection within the brains of acquired immune deficiency syndrome patients. Proc Natl AcadSci USA 1986;83:70897093.CrossRefGoogle ScholarPubMed
68. Takahashi, K, Wesselingh, SL, Griffin, DE, et al. Localization of HIV-1 in human brain using polymerase chain reaction/in situ hybridization and immunocytochemistry. Ann Neurol 1996;39:705711.CrossRefGoogle ScholarPubMed
69. Kure, K, Weidenheim, KM, Lyman, WD, et al. Morphology anddistribution of HIV-1 gp41-positive microglia in subacute AIDS encephalitis. Pattern of involvement resembling a multisystemdegeneration. Acta Neuropathol 1990;80:393400.CrossRefGoogle Scholar
70. Shaw, GM, Harper, ME, Hahn, BH, et al. HTLV-III infection inbrains of children and adults with AIDS encephalopathy. Science 1985;227:177182.CrossRefGoogle ScholarPubMed
71. Bagasra, O, Lavi, E, Bobroski, L, et al. Cellular reservoirs of HIV-1in the central nervous system of infected individuals: identification by the combination of in situ polymerase chain reaction and immunohistochemistry. AIDS 1996;10:573585.CrossRefGoogle Scholar
72. Nuovo, GJ, Gallery, F, MacConnell, P, et al. In situ detection ofpolymerase chain reaction-amplified HIV-1 nucleic acids and tumor necrosis factor-alpha RNA in the central nervous system. Am J Pathol 1994;144:659666.Google Scholar
73. Moses, AV, Bloom, FE, Pauza, CD, et al. Human immunodeficiencyvirus infection of human brain capillary endothelial cells occurs via a CD4/galactosylceramide-independent mechanism. Proc Natl Acad Sci USA 1993;90:1047410478.CrossRefGoogle Scholar
74. Poland, SD, Rice, GP, Dekaban, GA. HIV-1 infection of humanbrain-derived microvascular endothelial cells in vitro. J Acquir Immune Defic Syndr Hum Retrovirol 1995;8:437445.CrossRefGoogle ScholarPubMed
75. Gyorkey, F, Melnick, JL, Gyorkey, P. Human immunodeficiencyvirus in brain biopsies of patients with AIDS and progressiveencephalopathy. J Infect Dis 1987;155:870876.CrossRefGoogle Scholar
76. Obregon, E, Punzon, C, Fernandez-Cruz, E, et al. HIV-1 infectioninduces differentiation of immature neural cells through autocrine tumor necrosis factor and nitric oxide production. Virology 1999;261:193204.CrossRefGoogle ScholarPubMed
77. Ensoli, F, Cafaro, A, Fiorelli, V, et al. HIV-1 infection of primaryhuman neuroblasts. Virology 1995;210:221225.CrossRefGoogle ScholarPubMed
78. Feng, Y, Broder, CC, Kennedy, PE, et al. HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G proteincoupled receptor. Science 1996;272:872877.CrossRefGoogle Scholar
79. Alkhatib, G, Combadiere, C, Broder, CC, et al. CC CKR5: aRANTES, MIP-1alpha, MIP-1beta receptor as a fusion cofactorfor macrophage-tropic HIV-1. Science 1996; 272: 1955-1958.Google Scholar
80. He, J, Chen, Y, Farzan, M, et al. CCR3 and CCR5 are co-receptorsfor HIV-1 infection of microglia. Nature 1997;385:645649.CrossRefGoogle ScholarPubMed
81. Watkins, BA, Dorn, HH, Kelly, WB, et al. Specific tropism of HIV-1 for microglial cells in primary human brain cultures. Science 1990;249:549553.CrossRefGoogle ScholarPubMed
82. Power, C, McArthur, JC, Johnson, RT, et al. Distinct HIV-1 envsequences are associated with neurotropism and neurovirulence. Curr Top Microbiol Immunol 1995;202:89104.Google ScholarPubMed
83. Jordan, CA, Watkins, BA, Kufta, C, et al. Infection of brainmicroglial cells by human immunodeficiency virus type 1 is CD4 dependent. J Virol 1991;65:736742.Google ScholarPubMed
84. Chan, SY, Speck, RF, Power, C, et al. V3 recombinants indicate acentral role for CCR5 as a coreceptor in tissue infection by human immunodeficiency virus type 1. J Virol 1999;73:23502358.Google Scholar
85. Strizki, JM, Albright, AV, Sheng, H, et al. Infection of primary humanmicroglia and monocyte-derived macrophages with human immunodeficiency virus type 1 isolates: evidence of differentialtropism. J Virol 1996;70:76547662.Google Scholar
86. Chesebro, B, Wehrly, K, Nishio, J, et al. Macrophage-tropic humanimmunodeficiency virus isolates from different patients exhibit unusual V3 envelope sequence homogeneity in comparison with T-cell-tropic isolates: definition of critical amino acids involvedin cell tropism. J Virol 1992;66:65476554.Google Scholar
87. Kwong, PD, Wyatt, R, Robinson, J, et al. Structure of an HIV gp120envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody. Nature 1998;393:648659.CrossRefGoogle Scholar
88. Sanders, VJ, Pittman, CA, White, MG, et al. Chemokines andreceptors in HIV encephalitis. AIDS 1998;12:10211026.CrossRefGoogle ScholarPubMed
89. Zheng, J, Ghorpade, A, Niemann, D, et al. Lymphotropic virionsaffect chemokine receptor-mediated neural signaling and apoptosis: implications for human immunodeficiency virus type 1-associated dementia. J Virol 1999;73:82568267.Google ScholarPubMed
90. Kaul, M, Lipton, SA. Chemokines and activated macrophages inHIV gp120-induced neuronal apoptosis. Proc Natl Acad Sci USA 1999;96:82128216.CrossRefGoogle Scholar
91. Harouse, JM, Bhat, S, Spitalnik, SL, et al. Inhibition of entry of HIV-1 in neural cell lines by antibodies against galactosyl ceramide. Science 1991;253:320323.CrossRefGoogle ScholarPubMed
92. Ma, M, Geiger, JD, Nath, A. Characterization of a novel binding sitefor the human immunodeficiency virus type 1 envelope proteingp 120 on human fetal astrocytes. J Virol 1994;68:68246828.Google Scholar
93. Chesebro, B, Nishio, J, Perryman, S, et al. Identification of humanimmunodeficiency virus envelope gene sequences influencing viral entry into CD4-positive HeLa cells, T-leukemia cells, andmacrophages. J Virol 1991;65:57825789.Google Scholar
94. Westervelt, P, Trowbridge, DB, Epstein, LG, et al. Macrophagetropism determinants of human immunodeficiency virus type 1in vivo. J Virol 1992;66:25772582.Google Scholar
95. Morris, A, Marsden, M, Halcrow, K, et al. Mosaic structure of thehuman immunodeficiency virus type 1 genome infecting lymphoid cells and the brain: evidence for frequent in vivo recombination events in the evolution of regional populations. J Virol 1999;73:87208731.Google Scholar
96. Mayne, M, Bratanich, AC, Chen, P, et al. HIV-1 tat moleculardiversity and induction of TNF-alpha: implications for HIV-induced neurological disease. Neuroimmunomodulation 1998;5:184192.CrossRefGoogle ScholarPubMed
97. Corboy, JR, Buzy, JM, Zink, MC, et al. Expression directed fromHIV long terminal repeats in the central nervous system of transgenic mice. Science 1992;258:18041808.CrossRefGoogle ScholarPubMed
98. Wong, JK, Ignacio, CC, Torriani, F, et al. In vivocompartmentalization of human immunodeficiency virus: evidence from the examination of pol sequences from autopsytissues. J Virol 1997;71: 20592071.Google Scholar
99. Zhang, K, Hawken, M, Rana, F, et al. Human immunodeficiencyVirus type 1 Clade A and neurotropism: molecular evolution, recombination and co-receptor utilization. Virology 2001;283:1930.CrossRefGoogle Scholar
100. Kanki, PJ, Hamel, DJ, Sankale, JL, et al. Human immunodeficiencyvirus type 1 subtypes differ in disease progression. J Infect Dis 1999;179:68–73.CrossRefGoogle Scholar
101. Drosopoulos, WC, Rezende, LF, Wainberg, MA, et al. Virtues ofbeing faithful: can we limit the genetic variation in human immunodeficiency virus? J Mol Med 1998;76:604612.CrossRefGoogle Scholar
102. Kimata, JT, Kuller, L, Anderson, DB, et al. Emerging cytopathic andantigenic simian immunodeficiency virus variants influence AIDS progression. Nat Med 1999;5:535541.CrossRefGoogle ScholarPubMed
103. Hughes, ES, Bell, JE, Simmonds, P. Investigation of the dynamics ofthe spread of human immunodeficiency virus to brain and other tissues by evolutionary analysis of sequences from the p17gagand env genes. J Virol 1997;71:12721280.Google Scholar
104. Power, C, Buist, R, Johnston, JB, et al. Neurovirulence in felineimmunodeficiency virus-infected neonatal cats is viral strain specific and dependent on systemic immune suppression. J Virol 1998;72:91099115.Google ScholarPubMed
105. Phillips, TR, Prospero-Garcia, O, Puaoi, DL, et al. Neurologicalabnormalities associated with feline immunodeficiency virusinfection. J Gen Virol 1994;75:979987.CrossRefGoogle Scholar
106. Mankowski, JL, Flaherty, MT, Spelman, JP, et al. Pathogenesis ofsimian immunodeficiency virus encephalitis: viral determinantsof neurovirulence. J Virol 1997;71:60556060.Google Scholar
107. Mankowski, JL, Spelman, JP, Ressetar, HG, et al. Neurovirulentsimian immunodeficiency virus replicates productively in endothelial cells of the central nervous system in vivo and invitro. J Virol 1994;68:82028208.Google Scholar
108. Johnston, JB, Jiang, Y, van Marle, G, et al. Lentiviral infection in thebrain induce matrix metalloproteinase expression: the role of envelope diversity. J Virol 2000;74:72117220.CrossRefGoogle Scholar
109. Power, C, McArthur, JC, Nath, A, et al. Neuronal death induced bybrain-derived human immunodeficiency virus type 1 envelope genes differs between demented and nondemented AIDSpatients. J Virol 1998;72:90459053.Google Scholar
110. Smit, TK, Wang, B, Ng, T, et al. Varied tropism of HIV-1 isolatesderived from different regions of adult brain cortex discriminate between patients with and without AIDS dementia complex (ADC): evidence for neurotropic HIV variants. Virology 2001;279:509526.CrossRefGoogle ScholarPubMed
111. Smith, K, Crandall, KA, Kneissl, ML, et al. PCR detection of host and HIV-1 sequences from archival brain tissue. J Neurovirology 2000;6:164171.CrossRefGoogle ScholarPubMed
112. Ohagen, A, Ghosh, S, He, J, et al. Apoptosis induced by infection ofprimary brain cultures with diverse human immunodeficiency virus type 1 isolates: evidence for a role of the envelope. J Virol 1999;73:897906.Google Scholar
113. Nath, A, Geiger, J. Neurobiological aspects of humanimmunodeficiency virus infection: neurotoxic mechanisms. ProgNeurobiol 1998;54:1933.Google Scholar
114. Dreyer, EB, Kaiser, PK, Offermann, JT, et al. HIV-1 coat proteinneurotoxicity prevented by calcium channel antagonists. Science 1990;248:364367.CrossRefGoogle ScholarPubMed
115. Kaiser, PK, Offermann, JT, Lipton, SA. Neuronal injury due to HIV-1 envelope protein is blocked by anti-gp120 antibodies but notby anti-CD4 antibodies. Neurology 1990;40:17571761.CrossRefGoogle ScholarPubMed
116. Barks, JD, Liu, XH, Sun, R, et al. gp120, a human immunodeficiencyvirus-1 coat protein, augments excitotoxic hippocampal injury in perinatal rats. Neuroscience 1997;76:397409.Google ScholarPubMed
117. Giulian, D, Wendt, E, Vaca, K, et al. The envelope glycoprotein ofhuman immunodeficiency virus type 1 stimulates release of neurotoxins from monocytes. Proc Natl Acad Sci USA 1993; 90:27692773.CrossRefGoogle Scholar
118. Pattarini, R, Pittaluga, A, Raiteri, M. The human immunodeficiencyvirus-1 envelope protein gp120 binds through its V3 sequence to the glycine site of N-methyl-D-aspartate receptors mediating noradrenaline release in the hippocampus. Neuroscience 1998;87:147157.CrossRefGoogle ScholarPubMed
119. Lipton, SA, Gendelman, HE. Seminars in medicine of the Beth IsraelHospital, Boston. Dementia associated with the acquired immunodeficiency syndrome. N Engl J Med 1995;332:934940.CrossRefGoogle ScholarPubMed
120. Lee, J, Zipfel, G, Choi, D. The changing landscape of ischaemicbrain injury mechanisms. Nature 1999; 399: A7-A14.CrossRefGoogle ScholarPubMed
121. Lipton, SA. Memantine prevents HIV coat protein-inducedneuronal injury in vitro. Neurology 1992;42:14031405.CrossRefGoogle ScholarPubMed
122. Bennett, BA, Rusyniak, DE, Hollingsworth, CK. HIV-1 gp120-induced neurotoxicity to midbrain dopamine cultures. Brain Res 1995;705:168176.CrossRefGoogle ScholarPubMed
123. Dawson, VL, Dawson, TM, Uhl, GR, et al. Humanimmunodeficiency virus type 1 coat protein neurotoxicity mediated by nitric oxide in primary cortical cultures. Proc NatlAcad Sci USA 1993;90:32563259.CrossRefGoogle Scholar
124. Toggas, SM, Masliah, E, Rockenstein, EM, et al. Central nervoussystem damage produced by expression of the HIV-1 coat protein gp120 in transgenic mice. Nature 1994;367:188193.CrossRefGoogle Scholar
125. Benos, DJ, McPherson, S, Hahn, BH, et al. Cytokines and HIVenvelope glycoprotein gp120 stimulate Na+/H+ exchange in astrocytes. J Biol Chem 1994;269:1381113816.Google ScholarPubMed
126. Shrikant, P, Benos, DJ, Tang, LP, et al. HIV glycoprotein 120enhances intercellular adhesion molecule-1 gene expression in glial cells. Involvement of Janus kinase/signal transducer and activator of transcription and protein kinase C signalingpathways. J Immunol 1996;156:13071314.Google Scholar
127. Adamson, DC, Wildemann, B, Sasaki, M, et al. Immunologic NOsynthase: elevation in severe AIDS dementia and induction byHIV-1 gp41. Science 1996;274:19171921.CrossRefGoogle Scholar
128. Nath, A, Psooy, K, Martin, C, et al. Identification of a humanimmunodeficiency virus type 1 Tat epitope that is neuroexcitatory and neurotoxic. J Virol 1996;70:14751480.Google Scholar
129. Chen P, Mayne M, Power C, et al. The Tat protein of HIV-1 inducestumor necrosis factor-alpha production. Implications for HIV-1-associated neurological diseases. J Biol Chem 1997;272: 2238522388.CrossRefGoogle Scholar
130. Nath, A, Conant, K, Chen, P, et al. Transient exposure to HIV-1 Tatprotein results in cytokine production in macrophages and astrocytes. A hit and run phenomenon. J Biol Chem 1999;274:1709817102.CrossRefGoogle ScholarPubMed
131. Conant, K, Garzino-Demo, A, Nath, A, et al. Induction of monocytechemoattractant protein-1 in HIV-1 Tat-stimulated astrocytes and elevation in AIDS dementia. Proc Natl Acad Sci USA 1998; 95:31173121.CrossRefGoogle Scholar
131a. Catani, MV, Corasaniti, MT, Navarra, M, et al. gp120 induces cell death in human neuroblastoma cells through the CXCR4 and CCR5 chemokine receptors J Neurochem 2000;74:23732379.CrossRefGoogle ScholarPubMed
132. Johnston, JB, Zhang, K, Silva, C, et al. HIV-1 Tat neurotoxicity isprevented by matrix metalloproteinase inhibitors. Ann Neurol 2001;49:230241.3.0.CO;2-O>CrossRefGoogle ScholarPubMed
133. Perelson, AS, Essunger, P, Cao, Y, et al. Decay characteristics ofHIV-1-infected compartments during combination therapy. Nature 1997;387:188191.CrossRefGoogle Scholar
134. Ellis, RJ, Hsia, K, Spector, SA, et al. Cerebrospinal fluid humanimmunodeficiency virus type 1 RNA levels are elevated in neurocognitively impaired individuals with acquired immunodeficiency syndrome. HIV Neurobehavioral ResearchCenter Group. Ann Neurol 1997;42:679688.CrossRefGoogle Scholar
135. Ellis, RJ, Gamst, AC, Capparelli, E, et al. Cerebrospinal fluid HIVRNA originates from both local CNS and systemic sources. Neurology 2000;54: 927936.CrossRefGoogle Scholar
136. Johnson, RT, Glass, JD, McArthur, JC, et al. Quantitation of humanimmunodeficiency virus in brains of demented and nondemented patients with acquired immunodeficiency syndrome. Ann Neurol 1996;39:392395.CrossRefGoogle Scholar
137. Lazarini, F, Seilhean, D, Rosenblum, O, et al. Humanimmunodeficiency virus type 1 DNA and RNA load in brains of demented and nondemented patients with acquired immunodeficiency syndrome. J Neurovirol 1997;3:299303.CrossRefGoogle Scholar
138. Royal, W, 3rd, Selnes, OA, Concha, M, et al. Cerebrospinal fluidhuman immunodeficiency virus type 1 (HIV-1) p24 antigenlevels in HIV-1-related dementia. Ann Neurol 1994;36:3239.CrossRefGoogle ScholarPubMed
139. Brew, BJ, Rosenblum, M, Cronin, K, et al. AIDS dementia complexand HIV-1 brain infection: clinical-virological correlations. AnnNeurol 1995;38:563570.Google Scholar
140. Vazeux, R, Lacroix-Ciaudo, C, Blanche, S, et al. Low levels ofhuman immunodeficiency virus replication in the brain tissue of children with severe acquired immunodeficiency syndromeencephalopathy. Am J Pathol 1992;140:137144.Google Scholar
141. Gonzalez-Scarano, F, Baltuch, G. Microglia as mediators ofinflammatory and degenerative diseases. Annu Rev Neurosci 1999;22:219240.CrossRefGoogle Scholar
142. Giulian, D, Vaca, K, Noonan, CA. Secretion of neurotoxins bymononuclear phagocytes infected with HIV-1. Science 1990; 250:15931596.CrossRefGoogle ScholarPubMed
143. Pulliam, L, Herndier, BG, Tang, NM, et al. Humanimmunodeficiency virus-infected macrophages produce soluble factors that cause histological and neurochemical alterations incultured human brains. J Clin Invest 1991;87:503512.CrossRefGoogle Scholar
144. Tardieu, M, Janabi, N. HIV-1 and the developing human nervoussystem: in vivo and in vitro aspects. Dev Neurosci 1994; 16:137144.CrossRefGoogle Scholar
145. Gendelman, HE, Persidsky, Y, Ghorpade, A, et al. Theneuropathogenesis of the AIDS dementia complex. AIDS 1997;11: S35-45.Google ScholarPubMed
146. Tyor, WR, Glass, JD, Griffin, JW, et al. Cytokine expression in thebrain during the acquired immunodeficiency syndrome. AnnNeurol 1992; 31: 349360.Google Scholar
147. Wesselingh, SL, Power, C, Glass, JD, et al. Intracerebral cytokinemessenger RNA expression in acquired immunodeficiency syndrome dementia. Ann Neurol 1993;33:576582.CrossRefGoogle ScholarPubMed
148. Gelbard, HA, Nottet, HS, Swindells, S, et al. Platelet-activatingfactor: a candidate human immunodeficiency virus type 1-induced neurotoxin. J Virol 1994;68: 46284635.Google Scholar
149. Merrill, JE, Chen, IS. HIV-1, macrophages, glial cells, and cytokinesin AIDS nervous system disease. FASEB J 1991;5:23912397.CrossRefGoogle Scholar
150. Wilt, SG, Milward, E, Zhou, JM, et al. In vitro evidence for a dualrole of tumor necrosis factor-alpha in human immunodeficiency virus type 1 encephalopathy. Ann Neurol 1995;37:381394.CrossRefGoogle ScholarPubMed
151. Fine, SM, Angel, RA, Perry, SW, et al. Tumor necrosis factor alphainhibits glutamate uptake by primary human astrocytes. Implications for pathogenesis of HIV-1 dementia. J Biol Chem 1996;271:1530315306.CrossRefGoogle ScholarPubMed
152. Westmoreland, SV, Kolson, D, Gonzalez-Scarano, F. Toxicity of TNFalpha and platelet activating factor for human NT2N neurons: a tissue culture model for human immunodeficiency virusdementia. J Neurovirol 1996;2:118126.CrossRefGoogle Scholar
153. Sippy, BD, Hofman, FM, Wallach, D, et al. Increased expression oftumor necrosis factor-alpha receptors in the brains of patients with AIDS. J Acquir Immune Defic Syndr Hum Retrovirol 1995;10: 511521.CrossRefGoogle Scholar
154. Boven, LA, Middel, J, Portegies, P, et al. Overexpression of nervegrowth factor and basic fibroblast growth factor in AIDS dementia complex. J Neuroimmunol 1999; 97: 154162.CrossRefGoogle Scholar
155. Triggiani, M, Oriente, A, de Crescenzo, G, et al. Biochemicalfunctions of a pool of arachidonic acid associated with triglycerides in human inflammatory cells. Int Arch AllergyImmunol 1995;107: 261263.CrossRefGoogle ScholarPubMed
156. Griffin, DE, Wesselingh, SL, McArthur, JC. Elevated central nervoussystem prostaglandins in human immunodeficiency virus-associated dementia. Ann Neurol 1994;35:592597.CrossRefGoogle Scholar
157. Genis, P, Jett, M, Bernton, EW, et al. Cytokines and arachidonicmetabolites produced during human immunodeficiency virus (HIV)-infected macrophage-astroglia interactions: implications for the neuropathogenesis of HIV disease. J Exp Med 1992; 176:17031718.CrossRefGoogle ScholarPubMed
158. Rothstein, JD, Dykes-Hoberg, M, Pardo, CA, et al. Knockout ofglutamate transporters reveals a major role for astroglial transport in excitotoxicity and clearance of glutamate. Neuron 1996;16:675686.CrossRefGoogle Scholar
159. Saito, K, Heyes, MP. Kynurenine pathway enzymes in brain.Properties of enzymes and regulation of quinolinic acidsynthesis. Adv Exp Med Biol 1996;398:485492.CrossRefGoogle Scholar
160. Moroni, F. Tryptophan metabolism and brain function: focus onkynurenine and other indole metabolites. Eur J Pharmacol 1999;375:87100.CrossRefGoogle ScholarPubMed
161. Sei, S, Saito, K, Stewart, SK, et al. Increased humanimmunodeficiency virus (HIV) type 1 DNA content and quinolinic acid concentration in brain tissues from patients withHIV encephalopathy. J Infect Dis 1995;172:638647.CrossRefGoogle Scholar
162. Heyes, MP, Brew, BJ, Martin, A, et al. Quinolinic acid incerebrospinal fluid and serum in HIV-1 infection: relationship to clinical and neurological status. Ann Neurol 1991;29:202209.CrossRefGoogle Scholar
163. Conant, K, McArthur, JC, Griffin, DE, et al. Cerebrospinal fluidlevels of MMP-2, 7, and 9 are elevated in association with human immunodeficiency virus dementia. Ann Neurol 1999; 46:391398.3.0.CO;2-0>CrossRefGoogle ScholarPubMed
164. Yong, VW, Krekoski, CA, Forsyth, PA, et al. Matrixmetalloproteinases and diseases of the CNS. Trends Neurosci 1998;21:7580.CrossRefGoogle Scholar
165. Rostasy, K, Monti, L, Yiannoutsos, C, et al. Humanimmunodeficiency virus infection, inducible nitric oxide synthase expression, and microglial activation: pathogenetic relationship to the acquired immunodeficiency syndrome dementia complex. Ann Neurol 1999;46:207216.3.0.CO;2-4>CrossRefGoogle Scholar
166. Boven, LA, Gomes, L, Hery, C, et al. Increased peroxynitrite activityin AIDS dementia complex: implications for the neuropathogenesis of HIV-1 infection. J Immunol 1999;162:43194327.Google Scholar
167. Giulian, D, Yu, J, Li, X, et al. Study of receptor-mediated neurotoxinsreleased by HIV-1-infected mononuclear phagocytes found inhuman brain. J Neurosci 1996; 16:31393153.CrossRefGoogle Scholar
168. Ransohoff, RM, Tani, M. Do chemokines mediate leukocyterecruitment in post-traumatic CNS inflammation? Trends Neurosci 1998;21:154159.CrossRefGoogle ScholarPubMed
169. Kelder, W, McArthur, JC, Nance-Sproson, T, et al. Beta-chemokinesMCP-1 and RANTES are selectively increased in cerebrospinal fluid of patients with human immunodeficiency virus- associateddementia. Ann Neurol 1998;44:831835.CrossRefGoogle Scholar
170. Meucci, O, Fatatis, A, Simen, AA, et al. Chemokines regulatehippocampal neuronal signaling and gp120 neurotoxicity. Proc Natl Acad Sci USA 1998;95:1450014505.CrossRefGoogle ScholarPubMed
171. Corder, EH, Robertson, K, Lannfelt, L, et al. HIV-infected subjectswith the E4 allele for APOE have excess dementia and peripheralneuropathy. Nat Med 1998;4:11821184.CrossRefGoogle Scholar
171a. Quasney, MW, Zhang, Q, Sargent, S, et al. Increased frequency of the tumor necrosis factor-alpha-308 A allele in adults with human immunodeficiency virus dementia. Ann Neurol 2001 50:157162.CrossRefGoogle ScholarPubMed
172. Boven, LA, van der Bruggen, T, Sweder van Asbeck, B, et al. Potential role of CCR5 polymorphism in the development of AIDS dementia complex. FEMS Immunol Med Microbiol 1999;26:243247.CrossRefGoogle ScholarPubMed
173. Van Rij, RP, Portegies, P, Hallaby, T, et al. Reduced prevalence of theCCR5 delta32 heterozygous genotype in human immunodeficiency virus-infected individuals with AIDS dementiacomplex. J Infect Dis 1999;180:854857.CrossRefGoogle Scholar
174. Arthos, J, Rubbert, A, Rabin, RL, et al. CCR5 signal transduction inmacrophages by human immunodeficiency virus and simian immunodeficiency virus envelopes. J Virol 2000;74:64186424.CrossRefGoogle ScholarPubMed
175. O’Brien, SJ, Nelson, GW, Winkler, CA, et al. Polygenic andmultifactorial disease gene association in man: lessons from AIDS. Annu Rev Genet 2000; 34:563591.CrossRefGoogle Scholar
176. Nicotera, P, Lipton, SA Excitotoxins in neuronal apoptosis andnecrosis. J Cereb Blood Flow Metab 1999;19:583591.CrossRefGoogle Scholar
177. Everall, IP, Glass, JD, McArthur, J, et al. Neuronal density in thesuperior frontal and temporal gyri does not correlate with the degree of human immunodeficiency virus-associated dementia. Acta Neuropathol 1994;88:538544.CrossRefGoogle Scholar
178. Wiley, CA, Masliah, E, Morey, M, et al. Neocortical damage during HIV infection. Ann Neurol 1991;29:651657.CrossRefGoogle ScholarPubMed
179. Ketzler, S, Weis, S, Haug, H, et al. Loss of neurons in the frontalcortex in AIDS brains. Acta Neuropathol 1990;80:9294.CrossRefGoogle ScholarPubMed
180. Everall, IP, Heaton, RK, Marcotte, TD, et al. Cortical synapticdensity is reduced in mild to moderate human immunodeficiency virus neurocognitive disorder. HNRC Group. HIV Neuro-behavioral Research Center. Brain Pathol 1999;9:209217.CrossRefGoogle Scholar
181. Fox, L, Alford, M, Achim, C, et al. Neurodegeneration ofsomatostatin-immunoreactive neurons in HIV encephalitis. J Neuropathol Exp Neurol 1997;56:360368.CrossRefGoogle ScholarPubMed
182. Gelbard, HA, James, HJ, Sharer, LR, et al. Apoptotic neurons inbrains from paediatric patients with HIV-1 encephalitis and progressive encephalopathy. Neuropathol Appl Neurobiol 1995;21:208217.CrossRefGoogle ScholarPubMed
183. Adle-Biassette, H, Levy, Y, Colombel, M, et al. Neuronal apoptosisin HIV infection in adults. Neuropathol Appl Neurobiol 1995;21:218227.CrossRefGoogle Scholar
184. Adle-Biassette, H, Chretien, F, Wingertsmann, L, et al. Neuronalapoptosis does not correlate with dementia in HIV infection but is related to microglial activation and axonal damage. Neuropathol Appl Neurobiol 1999;25:123133.CrossRefGoogle Scholar
185. He, J, de Castro, CM, Vandenbark, GR, et al. Astrocyte apoptosisinduced by HIV-1 transactivation of the c-kit protooncogene. Proc Natl Acad Sci USA 1997;94:39543959.CrossRefGoogle Scholar
185a. Thompson, KA, McArthur, JC, Wesselingh, SL. Correlation between neurological progression and astrocyte apoptosis in HIV-associated dementia. Ann Neurol 2001 49:745752.CrossRefGoogle ScholarPubMed
186. Lannuzel, A, Barnier, JV, Hery, C, et al. Human immunodeficiencyvirus type 1 and its coat protein gp120 induce apoptosis and activate JNK and ERK mitogen-activated protein kinases in human neurons. Ann Neurol 1997;42:847856.CrossRefGoogle Scholar
187. Maggirwar, SB, Tong, N, Ramirez, S, et al. HIV-1 Tat-mediatedactivation of glycogen synthase kinase-3beta contributes to Tatmediated neurotoxicity. J Neurochem 1999;73:578586.CrossRefGoogle ScholarPubMed
188. Clifford, DB. Human immunodeficiency virus-associated dementia. Arch Neurol 2000;57:321324.CrossRefGoogle ScholarPubMed
189. Price, RW, Yiannoutos, T, Clifford, DB, et al. Neurological outcomesin late HIV infection:adverse impact of neurological survival and protection effect of antiretroviral therapy. AIDS 1999;13:16771685.CrossRefGoogle Scholar
190. Dore, GJ, Correll, PK, Li, Y, et al. Changes to AIDS dementiacomplex in the era of highly active antiretroviral therapy. AIDS 1999;13:12491253.CrossRefGoogle ScholarPubMed
191. Ferrando, S, van Gorp, W, McElhiney, M, et al. Highly activeantiretroviral treatment in HIV infection: benefits for neuropsychological function. AIDS 1998;12: F65-70.CrossRefGoogle ScholarPubMed
192. Tozzi, V, Balestra, P, Galgani, S, et al. Positive and sustained effectsof highly active antiretroviral therapy on HIV-1-associated neurocognitive impairment [In Process Citation]. AIDS 1999;13:18891897.CrossRefGoogle Scholar
193. Sacktor, NC, Lyles, RH, Skolasky, RL, et al. Combinationantiretroviral therapy improves psychomotor speed performance in HIV-seropositive homosexual men. Multicenter AIDS CohortStudy (MACS). Neurology 1999;52:16401647.CrossRefGoogle Scholar
194. Brew, BJ, Halman, MH, Catalan, J, et al. Abacavir in AIDS dementiacomplex: efficacy and lessons for future trials. AIDS, submitted.Google Scholar
195. Harrigan, PR, Alexander, CS. Selection of drug-resistant HIV[published erratum appears in trends Microbiol 1999 Jul;7(7):302]. Trends Microbiol 1999;7:120123.CrossRefGoogle Scholar
196. Hirsch, MS, Conway, B, D’Aquila, RT, et al. Antiretroviral drugresistance testing in adults with HIV infection: implications for clinical management. International AIDS Society – USA Panel. JAMA 1998;279:19841991.CrossRefGoogle Scholar
197. Bratanich, AC, Liu, C, McArthur, JC, et al. Brain-derived HIV-1 tatsequences from AIDS patients with dementia show increased molecular heterogeneity. J Neurovirol 1998;4:387393.CrossRefGoogle ScholarPubMed
198. McArthur, JC, Yiannoutsos, C, Simpson, DM, et al. A phase II trialof nerve growth factor for sensory neuropathy associated with HIV infection. AIDS Clinical Trials Group Team 291 [published erratumappears in Neurology 2000 Jul 13;55(1):162]. Neurology 2000;54:10801088.CrossRefGoogle Scholar
199. Schifitto, G, Sacktor, N, Marder, K, et al. Randomized trial of theplatelet-activating factor antagonist lexipafant in HIV-associated cognitive impairment. Neurological AIDS Research Consortium. Neurology 1999;53:391396.CrossRefGoogle ScholarPubMed
200. Navia, BA, Dafni, U, Simpson, D, et al. A phase I/II trial ofnimodipine for HIV-related neurologic complications. Neurology 1998;51:221228.CrossRefGoogle ScholarPubMed
You have Access
Cited by