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INTEGRASE INHIBITORS ARE AN INDEPENDENT RISK FACTOR FOR IRIS: AN ATHENA COHORT STUDY
Ingeborg Wijting1, Casper Rokx1, Ferdinand Wit2, Anneloes Postma1, Andy Hoepelman3, Ineke van der Ende1, Peter Reiss2, Bart Rijnders1
1Erasmus Univ Med Cntr, Rotterdam, Netherlands,2Stichting HIV Monitoring, Amsterdam, Netherlands,3Univ Med Cntr Utrecht, Utrect, Netherlands
Integrase inhibitors(II) are associated with an accelerated HIV-RNA decline and enhanced CD4 recovery. In late-presenters, these factors are associated with the immune reconstitution inflammatory syndrome (IRIS), a pathological immune reaction against antigens of opportunistic infections (OI). Whether the use of II containing cART is a risk factor for IRIS is unknown as phase-III trials of licensed II included few late presenters.
Observational study within the ATHENA cohort. Case finding by full chart review was done in all treatment-naïve patients initiating cART from 2009 onwards who were at increased risk for IRIS: those with CD4 ≤200cells/mm3, who were diagnosed with PCP, toxoplasmosis, Kaposi's sarcoma, CMV disease, cryptococcosis, mycobacterial disease or PML and/or initiated corticosteroids ≤12months after cART-initiation and/or died ≤12months after cART-initiation. 2 definitions of IRIS were used: IRIS criteria by French (=French IRIS) and IRIS diagnosed by the treating physician(=clinical IRIS). Patient charts were reviewed for both definitions using a standardized CRF. The 2 primary outcomes were French IRIS and combined clinical or French IRIS. Cox regression was used to compare the risk of IRIS in II and non-II users, while controlling for potential confounders. Patients were censored when switching from INI to non-INI or vice versa.
369 of 3250 patients initiating first-line cART fulfilled in- and exclusion criteria for chart review with a mean viral load and CD4 count of 275423c/ml and 38cells/mm3. Most prevalent OI were PCP (N=172), Candidiasis (N=143), Mycobacterial infections (N=51) and Kaposi's sarcoma (N=38). Any form of IRIS was observed in 26/69 (38%) of II-users compared to 47/300 (16%) in the non-II users (OR 3.2, 95%CI 1.8-5.8) (Table). Cox regression showed that use of II was independently associated with French as well as any form of IRIS (HR 2.6, 95%CI 1.3-5.1, p=0.004 and HR 2.6, 95%CI 1.6-4.4, p=0.0001).
Patients diagnosed with an OI and a CD4-count ≤200cells/mm3 initiating II-based cART had a more than doubled incidence of IRIS. If confirmed in future studies, initiating II-based cART in late-presenters with OI may have to be revisited, especially in resource limited-settings.