Fatal Immune Restoration Disease in Human Immunodeficiency Virus Type 1--Infected Patients with Progressive Multifocal Leukoencephalopathy: Impact of Antiretroviral Therapy--Associated Immune Reconstitution

Safdar, Amar; Rubocki, Ronald J.; Horvath, Joseph A.; Narayan, Kailash K.; Waldron, Robert L.
November 2002
Clinical Infectious Diseases;11/15/2002, Vol. 35 Issue 10, p1250
Academic Journal
Immune reconstitution resulting from use of highly active antiretroviral therapy in patients infected with human immunodeficiency virus type 1 (HIV-1) has been associated with a significant decrease in infectious morbidity and with improved survival. Occasionally, patients with quiescent disease due to human cytomegalovirus or nontuberculous mycobacteria may experience paradoxical worsening due to "dysregulated" restitution of the immune system (that is, immune restoration disease [IRD]). Acquired immunodeficiency syndrome-related progressive multifocal leukoencephalopathy (PML) is uncommon and often improves with immune recovery. We describe 2 HIV-1-infected patients with PML that presented with paradoxical worsening after the patients had commenced active antiretroviral therapy. After they had a transient response to highdose corticosteroid therapy, both patients died of progressive neurological deterioration. IRD in these patients with PML was unexpected and occurred soon after they had started receiving active antiretroviral therapy, during the period of improved antigen-specific T-helper cell function. Predictors of patients' proclivity for these adverse events are uncertain. Evaluation of targeted immunomodulatory therapy directed towards disease-specific IRD is critical and may play an important role in improved survival for patients who are at risk.


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