Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

AIDS-related cytomegalovirus neurologic disease

Mark A Jacobson, MD
Section Editor
John G Bartlett, MD
Deputy Editor
Jennifer Mitty, MD, MPH


Cytomegalovirus (CMV) neurologic disease is an uncommon serious complication of AIDS, which can cause paralysis or rapidly fatal encephalitis. Prior to the availability of potent antiretroviral therapy (ART), CMV neurologic disease occurred in up to 2 percent of patients with AIDS [1], primarily in those with a CD4 count <50 cells/microL. However, the incidence of CMV neurologic disease has decreased since ART became available [2,3].

This topic will discuss AIDS-related CMV neurologic disease. Discussions of other CMV-related diseases in HIV-infected patients are found elsewhere. (See "Pathogenesis, clinical manifestations, and diagnosis of AIDS-related cytomegalovirus retinitis" and "Treatment of AIDS-related cytomegalovirus retinitis" and "AIDS-related cytomegalovirus gastrointestinal disease" and "Cytomegalovirus infection as a cause of pulmonary disease in HIV-infected patients".)


It is hypothesized that cytomegalovirus (CMV) end-organ disease results from the hematogenous spread of CMV. The presence of CMV in blood (as measured by culture, CMV DNA amplification, or antigen detection) is a risk factor for the development of CMV disease in patients with AIDS [4]. However, patients with viremia (eg, those with a positive blood CMV DNA test result) do not necessarily have invasive disease. (See 'Evaluation' below.)

Impaired CD4 cell function or number is the key immune deficit that permits uncontrolled CMV replication. Studies in transplant recipients and patients with AIDS indicate that CD4-dependent CMV-specific cytotoxic T lymphocyte activity is critical for preventing CMV replication and end-organ disease [5-7]. Although most cases of CMV disease occur in patients with a CD4 cell count <50 cells/microL, patients may be predisposed before such severe CD4 cell depletion occurs. As an example, in a longitudinal study, patients with AIDS who subsequently developed CMV disease had lower T-cell proliferative responses to CMV, both early and late, compared to patients who did not develop disease [8]. Genetic factors may also contribute to this predisposition, since low responses to CMV were more common in those with HLA-B44 and HLA-DR7.

Viral factors may also impact disease. CMV strains in the cerebrospinal fluid of HIV-infected patients with encephalitis may differ significantly from those strains present in the general population. A phylogenetic analysis suggests possible viral recombination events that may have an effect on neurovirulence [9].

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Nov 2017. | This topic last updated: Apr 24, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Gallant JE, Moore RD, Richman DD, et al. Incidence and natural history of cytomegalovirus disease in patients with advanced human immunodeficiency virus disease treated with zidovudine. The Zidovudine Epidemiology Study Group. J Infect Dis 1992; 166:1223.
  2. Baril, L, Jouan, M, Caumes, E, et al. The impact of highly active antiretroviral therapy on the incidence of CMV disease in AIDS patients (abstract #I-31). 37th Interscience Conference on Antimicrobial Agents and Chemotherapy, 1997; Toronto, Canada.
  3. Hammer SM, Squires KE, Hughes MD, et al. A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic millimeter or less. AIDS Clinical Trials Group 320 Study Team. N Engl J Med 1997; 337:725.
  4. Shinkai M, Bozzette SA, Powderly W, et al. Utility of urine and leukocyte cultures and plasma DNA polymerase chain reaction for identification of AIDS patients at risk for developing human cytomegalovirus disease. J Infect Dis 1997; 175:302.
  5. Rook AH, Manischewitz JF, Frederick WR, et al. Deficient, HLA-restricted, cytomegalovirus-specific cytotoxic T cells and natural killer cells in patients with the acquired immunodeficiency syndrome. J Infect Dis 1985; 152:627.
  6. Walter EA, Greenberg PD, Gilbert MJ, et al. Reconstitution of cellular immunity against cytomegalovirus in recipients of allogeneic bone marrow by transfer of T-cell clones from the donor. N Engl J Med 1995; 333:1038.
  7. Jacobson MA, Maecker HT, Orr PL, et al. Results of a cytomegalovirus (CMV)-specific CD8+/interferon- gamma+ cytokine flow cytometry assay correlate with clinical evidence of protective immunity in patients with AIDS with CMV retinitis. J Infect Dis 2004; 189:1362.
  8. Schrier RD, Freeman WR, Wiley CA, McCutchan JA. Immune predispositions for cytomegalovirus retinitis in AIDS. The HNRC Group. J Clin Invest 1995; 95:1741.
  9. Steininger C, Schmied B, Sarcletti M, et al. Cytomegalovirus genotypes present in cerebrospinal fluid of HIV-infected patients. AIDS 2005; 19:273.
  10. Arribas JR, Storch GA, Clifford DB, Tselis AC. Cytomegalovirus encephalitis. Ann Intern Med 1996; 125:577.
  11. Morgello S, Cho ES, Nielsen S, et al. Cytomegalovirus encephalitis in patients with acquired immunodeficiency syndrome: an autopsy study of 30 cases and a review of the literature. Hum Pathol 1987; 18:289.
  12. Said G, Lacroix C, Chemouilli P, et al. Cytomegalovirus neuropathy in acquired immunodeficiency syndrome: a clinical and pathological study. Ann Neurol 1991; 29:139.
  13. McCutchan JA. Cytomegalovirus infections of the nervous system in patients with AIDS. Clin Infect Dis 1995; 20:747.
  14. Silva CA, Oliveira AC, Vilas-Boas L, et al. Neurologic cytomegalovirus complications in patients with AIDS: retrospective review of 13 cases and review of the literature. Rev Inst Med Trop Sao Paulo 2010; 52:305.
  15. French MA, Lenzo N, John M, et al. Immune restoration disease after the treatment of immunodeficient HIV-infected patients with highly active antiretroviral therapy. HIV Med 2000; 1:107.
  16. Aboulafia DM, Taylor L. Vacuolar myelopathy and vacuolar cerebellar leukoencephalopathy: a late complication of AIDS after highly active antiretroviral therapy-induced immune reconstitution. AIDS Patient Care STDS 2002; 16:579.
  17. Small PM, McPhaul LW, Sooy CD, et al. Cytomegalovirus infection of the laryngeal nerve presenting as hoarseness in patients with acquired immunodeficiency syndrome. Am J Med 1989; 86:108.
  18. Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: Recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. http://aidsinfo.nih.gov/contentfiles/lvguidelines/adult_oi.pdf (Accessed on July 10, 2017).
  19. Clifford DB, Arribas JR, Storch GA, et al. Magnetic resonance brain imaging lacks sensitivity for AIDS associated cytomegalovirus encephalitis. J Neurovirol 1996; 2:397.
  20. Revello MG, Percivalle E, Sarasini A, et al. Diagnosis of human cytomegalovirus infection of the nervous system by pp65 detection in polymorphonuclear leukocytes of cerebrospinal fluid from AIDS patients. J Infect Dis 1994; 170:1275.
  21. Arribas JR, Clifford DB, Fichtenbaum CJ, et al. Level of cytomegalovirus (CMV) DNA in cerebrospinal fluid of subjects with AIDS and CMV infection of the central nervous system. J Infect Dis 1995; 172:527.
  22. Flood J, Drew WL, Miner R, et al. Diagnosis of cytomegalovirus (CMV) polyradiculopathy and documentation of in vivo anti-CMV activity in cerebrospinal fluid by using branched DNA signal amplification and antigen assays. J Infect Dis 1997; 176:348.
  23. Combination foscarnet and ganciclovir therapy vs monotherapy for the treatment of relapsed cytomegalovirus retinitis in patients with AIDS. The Cytomegalovirus Retreatment Trial. The Studies of Ocular Complications of AIDS Research Group in Collaboration with the AIDS Clinical Trials Group. Arch Ophthalmol 1996; 114:23.
  24. Martin DF, Sierra-Madero J, Walmsley S, et al. A controlled trial of valganciclovir as induction therapy for cytomegalovirus retinitis. N Engl J Med 2002; 346:1119.
  25. Jacobson MA, Stanley HD, Heard SE. Ganciclovir with recombinant methionyl human granulocyte colony-stimulating factor for treatment of cytomegalovirus disease in AIDS patients. AIDS 1992; 6:515.
  26. Jacobson MA, Gambertoglio JG, Aweeka FT, et al. Foscarnet-induced hypocalcemia and effects of foscarnet on calcium metabolism. J Clin Endocrinol Metab 1991; 72:1130.
  27. Studies of Ocular Complications of AIDS Research Group, AIDS Clinical Trials Group. Mortality in patients with the acquired immunodeficiency syndrome treated with either foscarnet or ganciclovir for cytomegalovirus retinitis. N Engl J Med 1992; 326:213.
  28. Parenteral cidofovir for cytomegalovirus retinitis in patients with AIDS: the HPMPC peripheral cytomegalovirus retinitis trial. A randomized, controlled trial. Studies of Ocular complications of AIDS Research Group in Collaboration with the AIDS Clinical Trials Group. Ann Intern Med 1997; 126:264.
  29. Lalezari JP, Stagg RJ, Kuppermann BD, et al. Intravenous cidofovir for peripheral cytomegalovirus retinitis in patients with AIDS. A randomized, controlled trial. Ann Intern Med 1997; 126:257.
  30. Cidofovir injection solution US prescribing information (revised July, 2015) http://dailymed.nlm.nih.gov/dailymed/index.cfm.
  31. Davis JL, Taskintuna I, Freeman WR, et al. Iritis and hypotony after treatment with intravenous cidofovir for cytomegalovirus retinitis. Arch Ophthalmol 1997; 115:733.
  32. Whitley RJ, Jacobson MA, Friedberg DN, et al. Guidelines for the treatment of cytomegalovirus diseases in patients with AIDS in the era of potent antiretroviral therapy: recommendations of an international panel. International AIDS Society-USA. Arch Intern Med 1998; 158:957.
  33. Jabs DA, Bolton SG, Dunn JP, Palestine AG. Discontinuing anticytomegalovirus therapy in patients with immune reconstitution after combination antiretroviral therapy. Am J Ophthalmol 1998; 126:817.
  34. Macdonald JC, Karavellas MP, Torriani FJ, et al. Highly active antiretroviral therapy-related immune recovery in AIDS patients with cytomegalovirus retinitis. Ophthalmology 2000; 107:877.
  35. Whitcup SM, Fortin E, Lindblad AS, et al. Discontinuation of anticytomegalovirus therapy in patients with HIV infection and cytomegalovirus retinitis. JAMA 1999; 282:1633.
  36. Macdonald JC, Torriani FJ, Morse LS, et al. Lack of reactivation of cytomegalovirus (CMV) retinitis after stopping CMV maintenance therapy in AIDS patients with sustained elevations in CD4 T cells in response to highly active antiretroviral therapy. J Infect Dis 1998; 177:1182.