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≥ 18 years HIV+, c ART-naïve First CM

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≥ 18 years HIV+, c ART-naïve First CM

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  1. Clinical and mycological determinants of Cryptococcosis-associated IRIS (C-IRIS)Chang CC, Elliott JE, Gosnell BI, Dorasamy AA, Omarjee S, Naranbhai V, Spelman T, Moosa MY-S, Mahabeer Y, Lim A, Carr W, Coovadia Y, Ndung’u T, Lewin SR, French MAChristina C Chang MB.BS, FRACP, PhD studentDepartment of Infectious Diseases, Alfred Hospital, Monash University, MelbourneHIV Pathogenesis Programme, University of KwaZulu Natal, DurbanTHSA20: The Rainbow of IRIS in HIV Infection Mini-SymposiumXIX International AIDS Conference 2012 – Washington D.C. Thursday 29 July 2012

  2. Ethics approval: UKZN BF 053/09, Monash Uni 2009001224, UWA RA/4/1/2541 Study protocol • ≥18 years • HIV+, cART-naïve • First CM Neurological Deterioration cART IntensiveAmpho 14 d Consolidation 400mg Fluconazole12 weeks Maintenance 200mg Fluconazole therapy Clinical assessment W00 W02 W04 W08 W12 W16 W20 W24 C-IRIS Not C-IRIS Indeterminate

  3. 25.5% of those who commenced cART developed C-IRIS in the first 24 weeks Patients enrolled n=130 Excluded n=2 Death prior to cART commencement n=19 Commenced on cART n=106 Lost to follow-up n=3 Neurological Deterioration n=43 (40.6%) No ND n=63 (59.4%) Any C-IRIS n=27 (25.5%) NDs without C-IRIS n=16 (15.1%)

  4. Predictors of C-IRIS (Cox-regression univariate analysis) Median (interquartile range)

  5. CSF cryptococcal culture negativity pre-cART commencement and increasing CD4 T-cell are significantly associated with decreased rates of C-IRIS • Multivariate analysis

  6. Summary and implications • Lower CD4+ T-cell count, reduced CSF cellularity and CSF protein and higher CSF cryptococcal burden at CM presentation are predictors of C-IRIS • CSF sterility pre-cART is associated with a 74% reduction in the rate of C-IRIS (p=0.002, HR 0.26, 95%CI 0.11-0.62) • Greater CD4+T-cell depletion and a higher pathogen load are predictors of C-IRIS on multivariate analysis • Earlier HIV testing and treatment and enhanced cryptococcal management practices to improve attainment of CSF cryptococcal sterility are necessary to reduce rates of C-IRIS

  7. Acknowledgements • School of Pathology and Laboratory Medicine, University of Western Australia • Prof MA French, Dr A Lim • Dept. of Infectious Diseases, Alfred Hospital, Monash University • Prof SR Lewin, Dr JH Elliott, Dr T Spelman • Microbiology Department, NHLS, IALCH • Miss AA Dorasamy, Prof Y Coovadia, Dr Y Mahabeer • Dept. of Infectious Diseases, King Edward Hospital, UKZN • Dr BI Gosnell, Prof MY-S Moosa • HIV Pathogenesis Programme • Prof T Ndung’u, Dr V Naranbhai, Dr WH Carr, Miss S Omarjee, Miss R Durgiah • Dept. of Medicine, medical, nursing, laboratory, radiology, nursing and support staff at KEH and UKZN • Laboratory staff at RK Khan and Wentworth hospitals • Prof S Levitz, University Massachusetts • Mrs L Cockle, Keyboard Training Concepts • Study participants and their families • REACH initiative grant 2007 • Australian Postgraduate Award 2009 • Australian NHMRC Postgraduate Scholarship 2010-2012 • ANZ trustees research grant 2009 • Pfizer neuroscience research grant 2010 • World AIDS XIX 2012 - NIAID travel support

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