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Immunopathogenesis of immune reconstitution disease in HIV patients responding to antiretroviral therapy

Kestens, Luca; Seddiki, Nabilab; Bohjanen, Paul Rc

Current Opinion in HIV and AIDS: July 2008 - Volume 3 - Issue 4 - p 419–424
doi: 10.1097/COH.0b013e328302ebbb
Immune restoration disease: Edited by Robert Colebunders and Martyn French

Purpose of review The aim of this article is to review the most recent literature regarding the immunopathogenesis of pathogen-associated immune reconstitution disease and to discuss the role of immune activation and various effector molecules and cells such as macrophages, effector and regulatory T cells, and natural killer cells in immune reconstitution disease.

Recent findings Many HIV patients receiving antiretroviral treatment develop immune reconstitution disease, which is characterized by exaggerated inflammatory immune responses to replicating or dead pathogens. In the majority of these cases, immune reconstitution disease is associated with restoration of pathogen-specific cellular immune responses involving CD4+ or CD8+ effector T cells. The precise conditions that trigger immune reconstitution disease have not yet been identified. Immune reconstitution disease patients have overt immune activation, which may be due to poor homeostatic control after the fast initial immune recovery in patients receiving antiretroviral therapy. Poor homeostatic control in immune reconstitution disease patients may be linked to unbalanced restoration of effector and regulatory T cells.

Summary Although the precise mechanism of immune reconstitution disease is not well understood, it is probably related to rapid restoration of pathogen-specific immune responses and poor homeostatic control that promote exaggerated immunopathological responses, especially if viable pathogens or pathogen debris are present at high concentrations.

aImmunology Unit, Department of Microbiology, Institute of Tropical Medicine, Antwerpen, Belgium

bNational Centre For HIV Epidemiology and Clinical Research, University of New South Wales and Centre For Immunology, Darlinghurst, Australia

cCenter for Infectious Diseases and Microbiology Translational Research, Departments of Microbiology and Medicine, University of Minnesota, Minneapolis, Minnesota, USA

Correspondence to Professor Dr Luc Kestens, Immunology Unit, Department of Microbiology, Institute of Tropical Medicine Antwerpen, Nationalestraat 155, B-2000 Antwerpen, Belgium Tel: +32 3247 6229; fax: +32 3247231; e-mail:

© 2008 Lippincott Williams & Wilkins, Inc.