Journal of NeuroVirology

, Volume 9, Supplement 1, pp 38–41

Progressive multifocal leukoencephalopathy in acquired immunodeficiency syndrome: Explaining the high incidence and disproportionate frequency of the illness relative to other immunosuppressive conditions



In the era of the AIDS pandemic, progressive multifocal leukoencephalopathy (PML) has ceased being a rare disease. Prevalence estimates from clinical and pathological series suggest that up to 5% of all HIV-infected persons will develop PML. The extraordinary frequency with which PML attends HIV infection vastly exceeds its appearance in association with other predisposing conditions and has resulted in it no longer being considered a rare disorder. Why PML appears to be far more common with AIDS than with other underlying immunosuppressive conditions remains unexplained. Potential explanations include an alteration of the CNS milieu by HIV facilitating JC viral entry into the brain and activation of the JCV by HIV proteins, e.g., tat, and by inflammatory byproducts of HIV infection. It is quite likely that multiple diverse mechanisms are at play.


AIDS brain demyelination HIV progressive multifocal leukoencephalopathy (PML) 


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  1. Antinori A, Ammassari A, et al (2001). Epidemiology and prognosis of AIDS-associated progressive multifocal leukoencephalopathy in the HAART era. J NeuroVirol 7: 323–328.PubMedCrossRefGoogle Scholar
  2. Astrom K, Mancall E, et al (1958). Progressive multifocal leukoencephalopathy. Brain 81: 93–127.PubMedCrossRefGoogle Scholar
  3. Bedri J, Weinstein W, et al (1983). Progressive multifocal leukoencephalopathy in acquired immunodeficiency syndrome. N Engl J Med 309: 492–493.PubMedCrossRefGoogle Scholar
  4. Berger JR, Chauhan A, et al (2001). Epidemiological evidence and molecular basis of interactions between HIV and JC virus. J NeuroVirol 7: 329–338.PubMedCrossRefGoogle Scholar
  5. Berger JR, Kaszovitz B, et al (1987). Progressive multifocal leukoencephalopathy associated with human immunodeficiency virus infection. A review of the literature with a report of sixteen cases. Ann Intern Med 107: 78–87.PubMedGoogle Scholar
  6. Berger JR, Pall L, et al (1998). Progressive multifocal leukoencephalopathy in patients with HIV infection. J NeuroVirol 4: 59–68.PubMedCrossRefGoogle Scholar
  7. Bernick C, Gregorios JB (1984). Progressive multifocal leukoencephalopathy in a patient with acquired immune deficiency syndrome. Arch Neurol 41: 780–782.PubMedGoogle Scholar
  8. Brooks BR, Walker DL (1984). Progressive multifocal leukoencephalopathy. Neurol Clin 2: 299–313.PubMedGoogle Scholar
  9. Centers for Disease Control and Prevention (CDC) (1997). Update: trends in AIDS incidence—United States, 1996. MMWR Morb Mortal Wkly Rep 46: 861–867.Google Scholar
  10. CDC (2002). U.S. HIV and AIDS cases reported through June 2001. HIV/AIDS Surveillance Rep 13: 1–41.Google Scholar
  11. Chi D, Henry J, et al (2000). The effects of HIV infection on endothelial function. Endothelium 7: 223–242.PubMedGoogle Scholar
  12. Couraud PO (1998). Infiltration of inflammatory cells through brain endothelium. Pathol Biol (Paris) 46: 176–180.Google Scholar
  13. Dubois V, Moret H, et al (1998). Prevalence of JC virus viraemia in HIV-infected patients with or without neurological disorders: a prospective study. J NeuroVirol 4: 539–544.PubMedCrossRefGoogle Scholar
  14. Dworkin MS, Wan PC, et al (1999). Progressive multifocal leukoencephalopathy: improved survival of human immunodeficiency virus-infected patients in the protease inhibitor era. J Infect Dis 180: 621–625.PubMedCrossRefGoogle Scholar
  15. Gillespie SM, Chang Y, et al (1991). Progressive multifocal leukoencephalopathy in persons infected with human immunodeficiency virus, San Francisco, 1981–1989. Ann Neurol 30: 597–604.PubMedCrossRefGoogle Scholar
  16. Ho JL, Poldre PA, et al (1984). Acquired immunodeficiency syndrome with progressive multifocal leukoencephalopathy and monoclonal B-cell proliferation. Ann Intern Med 100: 693–696.PubMedGoogle Scholar
  17. Holman RC, Janssen RS, et al (1991). Epidemiology of progressive multifocal leukoencephalopathy in the United States: analysis of national mortality and AIDS surveillance data [see comments]. Neurology 41: 1733–1736.PubMedGoogle Scholar
  18. Ives NJ, Gazzard BG, et al (2001). The changing pattern of AIDS-defining illnesses with the introduction of highly active antiretroviral therapy (HAART) in a London clinic. J Infect 42: 134–139.PubMedCrossRefGoogle Scholar
  19. Janssen RS (1997). Epidemiology and neuroepidemiology of human immunodeficiency virus infection. In: AIDS and the nervous system. Berger JR, Levy RM (eds). Lippincott-Raven: Philadelphia, PA, pp 13–37.Google Scholar
  20. Katz DA, Berger JR, et al (1994). Progressive multifocal leukoencephalopathy complicating Wiskott-Aldrich syndrome. Report of a case andreview of the literature of progressive multifocal leukoencephalopathy with other inherited immunodeficiency states. Arch Neurol 51: 422–426.PubMedGoogle Scholar
  21. Kure K, Llena JF, et al (1991). Human immunodeficiency virus-1 infection of the nervous system: an autopsy study of 268 adult, pediatric, and fetal brains. Hum Pathol 22: 700–710.PubMedCrossRefGoogle Scholar
  22. Kurtzke J, Kurland L (1983). The epidemiology of neurologic disease. In: Clinical Neurology. Harper & Row: Philadelphia, PA, pp 1–14.Google Scholar
  23. Lane JH, Sasseville VG, et al (1996). Neuroinvasion by simian immunodeficiency virus coincides with increased numbers of perivascular macrophages/microglia and intrathecal immune activation. J Neuro-Virol 2: 423–432.Google Scholar
  24. Maschke M, Kastrup O, et al (2000). Incidence and prevalence of neurological disorders associated with HIV since the introduction of highly active antiretroviral therapy (HAART). J Neurol Neurosurg Psychiatry 69: 376–380.PubMedCrossRefGoogle Scholar
  25. Messite J, Stillman S (1996). Accuracy of death certificate completion. JAMA 275: 794–796.PubMedCrossRefGoogle Scholar
  26. Miller JR, Barrett RE, et al (1982). Progressive multifocal leukoencephalopathy in a male homosexual with T-cell immune deficiency. N Engl J Med 307: 1436–1438.PubMedCrossRefGoogle Scholar
  27. Nath A (November 11, 2002). Personal communication regarding the absence of adhesion molecule expression in AIDS-associated PML brain sections.Google Scholar
  28. Persidsky Y (1999). Model systems for studies of leukocyte migration across the blood-brain barrier. J NeuroVirol 5: 579–590.PubMedCrossRefGoogle Scholar
  29. Sacktor N, RH Lyles, et al (2001). HIV-associated neurologic disease incidence changes: Multicenter AIDS Cohort Study, 1990–1998. Neurology 56: 257–260.PubMedGoogle Scholar
  30. Tate LG (1994). Personal communication regarding PML in the Broward Medical Examiner’s office.Google Scholar
  31. Tornatore C, Berger JR, et al (1992). Detection of JC virus DNA in peripheral lymphocytes from patients with and without progressive multifocal leukoencephalopathy. Ann Neurol 31: 454–462.PubMedCrossRefGoogle Scholar
  32. Williams KC, Hickey WF (1995). Traffic of hematogenous cells through the central nervous system. Curr Top Microbiol Immunol 202: 221–245.PubMedGoogle Scholar

Copyright information

© Journal of NeuroVirology, Inc. 2003

Authors and Affiliations

  1. 1.Department of NeurologyUniversity of Kentucky College of Medicine, Kentucky Clinic L-445LexingtonUSA

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