Immune reconstitution inflammatory syndrome in patients starting antiretroviral therapy for HIV infection: a systematic review and meta-analysis

Abstract

Summary This systematic review examines the incidence of Immune Reconstitution Disease (IRD) in HIV-1 infected patients starting antiretroviral combination therapy (ART). We analysed 13103 patients from 54 cohort studies; 1685 patients developed IRD. Pooled incidences with 95% credibility intervals (CrI) were calculated using Bayesian methods. In patients with previously diagnosed AIDS-defining conditions the incidence was 37.7% (95% CrI 26.6–49.4%) for CMV retinitis, 19.5% (6.7–44.8%) for cryptococcal meningitis, 15.7% (9.7–24.5%) for tuberculosis, 16.7% (2.3–50.7%) for progressive multifocal leukencephalopathy and 6.4% (1.2–24.7%) for Kaposi’s sarcoma. The incidence of any type of IRD, based on studies of unselected patients starting ART, was 16.1% (11.1–22.9%). Lethality was 4.5% (2.1–8.6%) for any type of IRD, 3.2% (0.7–9.2%) for tuberculosis and 20.8% (5.0–52.7%) for cryptococcal meningitis. Meta-regression analyses showed that the incidence is largely determined by the CD4 cell count at the start of ART, with a high risk in patients starting below 50 cells/μl. Many of the IRD events might therefore be prevented with earlier initiation of ART.

HIV-associated Hodgkin lymphoma during the first months on combination antiretroviral therapy

“…9 The possibility that HL could be triggered by immune reconstitution has not been established, but this is implied by the elevated risk of HL observed in the 3 months after cART initiation, which is the typical interval for IRIS to manifest. 15,16,32 Assessment of changes in EBV infection during immune reconstitution, such as increased expression of LMP-1 in germinal-center or circulating B cells, would support this possibility.…”

“…14 Moreover, within 6 months of starting cART, 10% or more of patients develop immune reconstitution inflammatory syndrome (IRIS). 15 Classically, IRIS is described as the appearance or progression of opportunistic infections, especially tuberculous and nontuberculous mycobacteria, cryptococcosis, uveitis, and progressive multifocal leukoencephalopathy, within weeks to months of cART initiation. 16 Myriad other conditions, both infectious and autoimmune and including systemic lupus erythematous, polymyositis, rheumatoid arthritis, and Graves disease, have been attributed to IRIS.…”

“…16 Myriad other conditions, both infectious and autoimmune and including systemic lupus erythematous, polymyositis, rheumatoid arthritis, and Graves disease, have been attributed to IRIS. 15 Considering the possibility that HL may be a manifestation of IRIS, the present study evaluated the risk of HL during the first months after cART initiation in an HIV-infected population followed in France using data from the French Hospital Database on HIV infection (FHDH-ANRS CO4), with careful modeling of the relationship between risk of HL and level of immunity as reflected by the CD4 cell count. …”

Treatment of CNS Vasculitis in Children

“…Many other viruses, bacteria, and fungal infections can cause secondary CNS vasculitis. Patients with HIV can also develop secondary CNS vasculitis based on infections due to immune reconstitution syndrome (IRIS) [48]. IRIS develops usually in the first 2 months after start of antiretroviral therapy.…”

Migration et pathogénicité des lymphocytes T CD8 dans les maladies du système nerveux central

“…Le début du traitement ARV chez des patients infectés par le VIH, et porteurs d'une leucoencéphalopathie multifocale progressive, est associé à la survenue d'une LEMP-SIRI (association des deux pathologies) dans 16,7 % (2,3 à 50,7 %) des cas [24]. L'interruption du traitement par natalizumab (habituellement suivie d'échanges plasmatiques visant à accélérer la clairance de l'anticorps) chez des patients traités pour une SEP et ayant développé une LEMP est, quant à elle, associée à la survenue d'une LEMP-SIRI chez la quasi-totalité des patients [25].…”