Immune reconstitution after potent antiretroviral therapy in AIDS patients with progressive multifocal leukoencephalopathy

Neurological disease is the initial manifestation of acquired immunodeficiency syndrome (AIDS) in 10–20% of patients with HIV infection. Progressive multifocal leukoencephalopathy (PML) predominantly involves the cerebral hemispheres, with a small subset of patients having lesions predominantly or exclusively confined to the cerebellum. The radiological features of PML are typically non-inflammatory. As a result of potent antiretroviral therapy (ART), however, inflammatory lesions are becoming more common in HIV-infected individuals and are due, in part, to immune reconstitution that occurs in recipients of potent ART. In the majority of such cases, the clinical outcome of immune reconstitution PML has been beneficial to the host, although several case reports have described worsening or fatal outcomes in PML patients as a result of potent ART. The following 2 cases of immune reconstitution PML described in this report illustrate the varied radiological manifestations and clinical outcomes that can develop in AIDS patients with PML receiving potent ART. Moreover, these cases highlight the inflammatory changes observed on neuroimaging in AIDS patients with immune reconstitution PML receiving potent ART and to our knowledge are the first reports of immune reconstitution isolated to the cerebellum in such patients.

[1]  F. Gray,et al.  Fulminant inflammatory leukoencephalopathy associated with HAART-induced immune restoration in AIDS-related progressive multifocal leukoencephalopathy , 2005, Acta Neuropathologica.

[2]  K. Tyler The uninvited guest , 2003, Neurology.

[3]  J. Delfraissy,et al.  Critical role of JC virus-specific CD4 T-cell responses in preventing progressive multifocal leukoencephalopathy , 2003, AIDS.

[4]  A. Safdar,et al.  Fatal immune restoration disease in human immunodeficiency virus type 1-infected patients with progressive multifocal leukoencephalopathy: impact of antiretroviral therapy-associated immune reconstitution. , 2002, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[5]  N. Letvin,et al.  JC Virus-Specific Cytotoxic T Lymphocytes in Individuals with Progressive Multifocal Leukoencephalopathy , 2001, Journal of Virology.

[6]  J. Collazos,et al.  Contrast-enhancing progressive multifocal leukoencephalopathy as an immune reconstitution event in AIDS patients. , 1999, AIDS.

[7]  C. Fichtenbaum,et al.  Progressive multifocal leukoencephalopathy in patients with AIDS receiving highly active antiretroviral therapy. , 1999, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[8]  D M Simpson,et al.  HAART improves prognosis in HIV-associated progressive multifocal leukoencephalopathy , 1999, Neurology.

[9]  R. Levy,et al.  Predictive factors for prolonged survival in acquired immunodeficiency syndrome—associated progressive multifocal leukoencephalopathy , 1998, Annals of neurology.

[10]  M. Narita,et al.  Paradoxical worsening of tuberculosis following antiretroviral therapy in patients with AIDS. , 1998, American journal of respiratory and critical care medicine.

[11]  W. Freeman,et al.  Immune recovery vitritis associated with inactive cytomegalovirus retinitis: a new syndrome. , 1998, Archives of ophthalmology.

[12]  N. Letvin,et al.  Focal mycobacterial lymphadenitis following initiation of protease-inhibitor therapy in patients with advanced HIV-1 disease , 1998, The Lancet.

[13]  T. Flanigan,et al.  2·5 year remission of AIDS-associated progressive multifocal leukoencephalopathy with combined antiretroviral therapy , 1997, The Lancet.

[14]  P. Kelly,et al.  Contrast-enhancing progressive multifocal leukoencephalopathy: radiological and pathological correlations: case report. , 1996, Neurosurgery.

[15]  C. Ryschkewitsch,et al.  Genotype profile of human polyomavirus JC excreted in urine of immunocompetent individuals , 1996, Journal of clinical microbiology.

[16]  G. Ault,et al.  Human polyomavirus JC promoter/enhancer rearrangement patterns from progressive multifocal leukoencephalopathy brain are unique derivatives of a single archetypal structure. , 1993, The Journal of general virology.

[17]  R. Holman,et al.  Epidemiology of progressive multifocal leukoencephalopathy in the United States , 1991, Neurology.