HIV infection: a systematic review and meta-analysisA

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

In patients with HIV-1 infection who are starting combination antiretroviral therapy, the incidence of immune reconstitution inflammatory syndrome (IRIS) is not well defined. The authors did a meta-analysis to establish the incidence and lethality of the syndrome in patients with a range of previously diagnosed opportunistic infections, and examined the relation between occurrence and the degree of immunodeficiency. Systematic review identified 54 cohort studies of 13 103 patients starting ART, of whom 1699 developed IRIS. They calculated pooled cumulative incidences with 95% credibility intervals (CrI) by Bayesian methods and did a random-effects metaregression to analyse the relation between CD4 cell count and incidence of IRIS. In patients with previously diagnosed AIDS-defining illnesses, IRIS developed in 37.7% (95% CrI 26.6-49.4) of those with cytomegalovirus retinitis, 19.5% (6.7-44.8) of those with cryptococcal meningitis, 15.7% (9.7-24.5) of those with tuberculosis, 16.7% (2.3-50.7) of those with progressive multifocal leukoencephalopathy, and 6.4% (1.2-24.7) of those with Kaposi's sarcoma, and 12.2% (6.8-19.6) of those with herpes zoster. 16.1% (11.1-22.9) of unselected patients starting antiretroviral therapy developed any type of IRIS. 4.5% (2.1-8.6) of patients with any type of IRIS died, 3.2% (0.7-9.2) of those with tuberculosis-associated IRIS died, and 20.8% (5.0-52.7) of those with cryptococcal meningitis died. Metaregression analyses showed that the risk of IRIS is associated with CD4 cell count at the start of antiretroviral therapy, with a high risk in patients with fewer than 50 cells per muL. Occurrence of IRIS might therefore be reduced by initiation of antiretroviral therapy before immunodeficiency becomes advanced.

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Editors’ note: Antiretroviral therapy gradually restores immune responses by suppressing HIV-1 replication and increasing CD4+ counts. Some people develop an immune reconstitution inflammatory syndrome (IRIS) when they start antiretroviral therapy either because their immune system develops an exaggerated activation against a persistent antigen (called paradoxical IRIS) or viable pathogens (called unmasking IRIS). This systematic review suggests that IRIS is more likely to occur when CD4 cell counts are low and in those who have a past history of cytomegalovirus retinitis, cryptococcal meningitis, and tuberculosis. The study of IRIS could teach us more about the immune system as IRIS appears to result from exaggerated and deregulated immune responses that vary depending on the associated pathogen. Little is known about treating IRIS although corticosteroids may be effective in extreme cases. What is clear is that the higher the CD4 count at initiation of antiretroviral treatment, the lower the risk of opportunistic infections and the lower the risk of IRIS.