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RESEARCH PRODUCT

The Downside of an Effective cART: The Immune Restoration Disease

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The prognosis of patients infected with human immunodeficiency virus (HIV) type 1 has dramatically improved since the advent of the highly active antiretroviral therapy (HAART), which have enabled sustained suppression of HIV replication and recovery of CD4+ T cells count [1-3]. However, many patients in resource-poor settings still start HAART at a late stage of HIV infection when they already have advanced immunodeficien‐ cy [4,5]. Immune reconstitution in HIV infected patients is characterized by replenishment of immune cells depleted directly or indirectly by HIV infection, by regeneration of primary and secondary lymphoid organs, by restoration of pathogen-specific T, B and NK cells and by a regulation of the reconstituted immune system [2]. It is unclear whether complete im‐ mune reconstitution ever occurs but individuals with human immunodeficiency virus infec‐ tion starting antiretroviral therapy when they are very immunodeficient are susceptible to immune reconstitution disorders. This phenomenon is known as a multitude of names in‐ cluding “immune reconstitution inflammatory syndrome (IRIS)”, “immune reconstitution or restoration disease” (IRD) or immune reconstitution syndrome” and includes various forms of a clinical deterioration as a consequence of a rapid and dysregulated restoration of anti‐ gen specific immune responses causing an exuberant inflammatory reaction and a cytokines storm [1-3]. This was first noted following the introduction of zidovudine monotherapy in the early 1990s, when localized forms of Mycobacterium avium intracellulare (MAI) infection where observed in association with the recovery rather than failure of cellular immune re‐ sponse [6]. Later, in 1992, French MA et al showed that the disease associated with Mycobac‐ terium avium complex (MAC) infection occurred after nucleoside analogue therapy and correlated with restoration of delayed hypersensitivity (DTH) responses to mycobacterial antigens [7].