Immune reconstitution inflammatory syndrome in Human Immunodeficiency Virus-infected patients treated with antiretroviral therapy

Abstract

Early antiretroviral therapy (ART) for Human Immunodeficiency Virus (HIV) infected people has led to a decrease in the risk of mortality and in the occurrence of opportunistic infections (OI). However, a non negligible proportion of patients will develop unusual and exaggerated inflammatory response to opportunistic pathogens named immune reconstitution inflammatory syndrome (IRIS). Paradoxical IRIS occurs in patients already efficiently treated for an OI, and who deteriorate after initiation of ART while unmasking IRIS occurs in patients who have already initiated ART and in whom a latent OI exists before ART initiation. IRIS requires the exclusion of any new OI, uncontrolled OI, and drug toxicity. IRIS is estimated to occur in 16% of the patients, with a low mortality, except for central nervous system IRIS. Risk factors for IRIS are advanced HIV infection, disseminated OI, early ART introduction after OI treatment, as well as rapid immune and viral response to ART. IRIS pathophysiology leading to excessive immune response is not well understood. Clinical manifestations of IRIS are diverse and related to the involved pathogen. Mycobacteria, cryptococcus, cytomegalovirus and JC virus are the main agents responsible for IRIS. IRIS treatment is not well established. Except for life-threatening IRIS, ART should not be discontinued. Steroids can be used for severe IRIS associated with tuberculosis and progressive multifocal leukoencephalopathy.