These are described in detail in the Methods section.
ReviewImmune reconstitution inflammatory syndrome in patients starting antiretroviral therapy for HIV infection: a systematic review and meta-analysis
Introduction
Combination antiretroviral therapy (ART) substantially reduces the occurrence of opportunistic events and mortality in patients with HIV.1 The beneficial effects of ART result from gradual restoration of pathogen-specific immune responses, mediated by suppressed HIV-1 replication and increased CD4 cell count.2, 3 WHO estimates that by the end of 2008 about 4 million people were receiving ART in countries of low and middle income—ten-times more than at the end of 2003.4 However, many patients in resource-poor settings start ART at a late stage when they already have advanced immunodeficiency.5, 6
Complications related to ART-induced immune reconstitution include paradoxical worsening of treated opportunistic infections or the unmasking of previously subclinical, untreated infections—so-called immune reconstitution inflammatory syndrome (IRIS), also known as immune reconstitution disease.7, 8, 9, 10 The panel summarises common definitions for IRIS. The syndrome is usually a consequence of exaggerated activation of the immune system against persistent antigen (paradoxical IRIS) or viable pathogens (unmasking IRIS), but it can also develop as progression of proliferative disease in patients with cancers.14 IRIS has been associated with a wide range of pathologies, including mycobacterial and cryptococcal infections, Kaposi's sarcoma, non-Hodgkin lymphoma, and progressive multifocal leukoencephalopathy.8, 9, 10, 15, 16, 17 Non-AIDS-defining illnesses such as sarcoidosis18 and rheumatic diseases19 can also transiently deteriorate after starting of ART.
The proportion of patients starting ART who develop IRIS is not well known, with estimates ranging from less than 10% to more than 50%.20, 21, 22, 23, 24 Several studies,10, 17, 25, 26, 27 but not all,21, 28, 29 have reported an increased risk of the syndrome in patients starting ART who have advanced immunodeficiency. We did a systematic review and meta-analysis of cohort studies to better define the incidence and lethality of IRIS in patients starting ART in countries of low, middle, and high income.
Section snippets
Search strategy and selection criteria
We searched Medline and Embase from January, 1996, to October, 2009, for published reports with the terms “immune reconstitution syndrome”, “immune reconstitution disease”, “immune restitution syndrome”, “immune restitution disease”, “immune reconstitution inflammatory syndrome”, and “immune recovery uveitis”. No language restrictions were used. Articles, brief reports, and letters to editors were included. Reference lists of relevant papers were screened. We also searched abstracts from
Results
The search identified 856 reports and 118 abstracts, of which 54 cohort studies from 22 countries were eligible for analysis: 22 (41%) were full-text reports, 21 (39%) were abstracts, and 11 (20%) were letters to the editor (figure 1, table 1). 17 cohorts (31%) were in unselected groups of people that included patients with and without AIDS, and studied any type of IRIS (table 1). The remaining studies were in patients with previously diagnosed opportunistic infections and examined paradoxical
Discussion
The incidence of IRIS among people starting ART varies with the AIDS-defining illness. The proportion of patients developing IRIS was highest in those with cytomegalovirus retinitis, high in those with cryptococcal meningitis, progressive multifocal leukoencephalopathy, or tuberculosis, and least common in those with Kaposi's sarcoma or herpes zoster. Differences in the incidence of IRIS between these opportunistic infections seem to be related to CD4 cell counts at baseline. In unselected
Search strategy and selection criteria
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