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
References (85)
- et al.
Long-term effectiveness of potent antiretroviral therapy in preventing AIDS and death: a prospective cohort study
Lancet
(2005) - et al.
Immunological recovery and antiretroviral therapy in HIV-1 infection
Lancet Infect Dis
(2006) - et al.
Immune reconstitution syndrome associated with opportunistic mycoses
Lancet Infect Dis
(2007) - et al.
Immune reconstitution disease associated with mycobacterial infections in HIV-infected individuals receiving antiretrovirals
Lancet Infect Dis
(2005) - et al.
Tuberculosis-associated immune reconstitution inflammatory syndrome: case definitions for use in resource-limited settings
Lancet Infect Dis
(2008) - et al.
Paradoxical worsening of tuberculosis in HIV-infected persons
Chest
(2001) - et al.
Rheumatic complications of human immunodeficiency virus infection in the era of highly active antiretroviral therapy: emergence of a new syndrome of immune reconstitution and changing patterns of disease
Semin Arthritis Rheum
(2005) - et al.
Statins for secondary prevention in elderly patients: a hierarchical bayesian meta-analysis
J Am Coll Cardiol
(2008) - et al.
Immune reconstitution inflammatory syndrome of tuberculosis among HIV-infected patients receiving antituberculous and antiretroviral therapy
J Infect
(2006) - et al.
Immune recovery uveitis in patients with AIDS and cytomegalovirus retinitis after highly active antiretroviral therapy
Am J Ophthalmol
(2000)
Immune reconstitution syndrome in the course of antiretroviral treatment in Senegal
Med Mal Infect
Positive effects of combined antiretroviral therapy on CD4+ T cell homeostasis and function in advanced HIV disease
Science
Towards universal access. Scaling up priority HIV/AIDS interventions in the health sector. 2009 progress report
Mortality of HIV-1-infected patients in the first year of antiretroviral therapy: comparison between low-income and high-income countries
Lancet
Antiretroviral therapy in resource-limited settings 1996 to 2006: patient characteristics, treatment regimens and monitoring in sub-Saharan Africa, Asia and Latin America
Trop Med Int Health
Immune reconstitution inflammatory syndrome: emergence of a unique syndrome during highly active antiretroviral therapy
Medicine
Immune restoration disease after antiretroviral therapy
AIDS
Immune recovery vitritis and uveitis in AIDS: clinical predictors, sequelae, and treatment outcomes
Retina
HIV/AIDS: immune reconstitution inflammatory syndrome: a reappraisal
Clin Infect Dis
The role of immune reconstitution inflammatory syndrome in AIDS-related Cryptococcus neoformans disease in the era of highly active antiretroviral therapy
Clin Infect Dis
Inflammatory reactions in HIV-1-infected persons after initiation of highly active antiretroviral therapy
Ann Intern Med
Tuberculosis immune reconstitution inflammatory syndrome in countries with limited resources
Int J Tuberc Lung Dis
Clinical course and prognostic factors of progressive multifocal leukoencephalopathy in patients treated with highly active antiretroviral therapy
Clin Infect Dis
Immune reconstitution inflammatory syndrome associated with Kaposi's sarcoma
J Clin Oncol
Incidence of immune reconstitution syndrome in HIV/tuberculosis-coinfected patients after initiation of generic antiretroviral therapy in India
J Acquir Immune Defic Syndr
Paradoxical worsening of tuberculosis following antiretroviral therapy in patients with AIDS
Am J Respir Crit Care Med
Cryptococcocal immune reconstitution disease: a major cause of early mortality in a South African antiretroviral programme
AIDS
Lower incidence and severity of cytomegalovirus-associated immune recovery uveitis in HIV-infected patients with delayed highly active antiretroviral therapy
AIDS
Immune restoration disease after the treatment of immunodeficient HIV-infected patients with highly active antiretroviral therapy
HIV Med
The prevalence and risk of immune restoration disease in HIV-infected patients treated with highly active antiretroviral therapy
HIV Med
Explosion of tuberculin-specific Th1-responses induces immune restoration syndrome in tuberculosis and HIV co-infected patients
AIDS
Determinants of immune reconstitution inflammatory syndrome in HIV type 1-infected patients with tuberculosis after initiation of antiretroviral therapy
Clin Infect Dis
Human development report
Bayesian approaches to clinical trials and health-care evaluations
Estimating the mean and variance from the median, range, and the size of a sample
BMC Med Res Methodol
Paradoxical reactions of tuberculosis in patients with the acquired immunodeficiency syndrome who are treated with highly active antiretroviral therapy
Arch Intern Med
Clinical characteristics of IRIS syndrome in patients with HIV and tuberculosis
Antivir Ther
Tuberculosis-associated immune reconstitution disease: incidence, risk factors and impact in an antiretroviral treatment service in South Africa
AIDS
Tuberculosis manifested by immune reconstitution inflammatory syndrome during HAART
AIDS
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