Clinical and mycological predictors of cryptococcosis-associated immune reconstitution inflammatory syndrome

• Published in: AIDS (London) Vol. 27; no. 13; pp. 2089 - 2099
• Main Authors: CHANG, Christina C, DORASAMY, Afton A, LEWIN, Sharon R, FRENCH, Martyn A, GOSNELL, Bernadett I, ELLIOTT, Julian H, SPELMAN, Tim, OMARJEE, Saleha, NARANBHAI, Vivek, COOVADIA, Yacoob, NDUNG'U, Thumbi, MOOSA, Mohamed-Yunus S
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 24.08.2013
• Subjects: Adult; AIDS/HIV; Anti-Retroviral Agents - administration & dosage; Antifungal Agents - administration & dosage; Biological and medical sciences; Biomarkers; CD4 Lymphocyte Count; Cerebrospinal Fluid - microbiology; Cohort Studies; Cryptococcosis - diagnosis; Cryptococcosis - pathology; Cryptococcus; Female; General aspects; HIV Infections - complications; HIV Infections - drug therapy; Human immunodeficiency virus; Human mycoses; Human viral diseases; Humans; Immune Reconstitution Inflammatory Syndrome - diagnosis; Immune Reconstitution Inflammatory Syndrome - pathology; Immunopathology; Infectious diseases; Longitudinal Studies; Male; Medical sciences; Miscellaneous mycoses; Mycoses; Prospective Studies; South Africa; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; South Africa; HIV/AIDS; Immunopathology; Nervous system diseases; Mycosis; cryptococcal meningitis; cryptococcosis-associated immune reconstitution inflammatory syndrome; Cryptococcosis; Retroviridae; Immune reconstitution; AIDS; Immune deficiency; Lentivirus; Infection; Virus; Immune reconstitution syndrome; Viral disease; Central nervous system disease; immune restoration disease; Meningitis; Human immunodeficiency virus; Predictive factor
• DOI: 10.1097/qad.0b013e3283614a8d
• ISSN: 0269-9370

HIV-infected patients with treated cryptococcal meningitis are at risk for further neurological deterioration after commencing combination antiretroviral therapy (cART), mostly because of cryptococcosis-associated immune reconstitution inflammatory syndrome (C-IRIS). Identifying predictors of C-IRIS could enable risk stratification. Prospective, longitudinal cohort study for 24 weeks. Durban, South Africa. One hundred and thirty HIV-infected patients with first cryptococcal meningitis episode : Antifungal therapy (amphotericin 1 mg/kg median 14 days, followed by consolidation and maintenance fluconazole) and cART (commenced median of 18 days from cryptococcal meningitis diagnosis). Clinical, blood, and cerebrospinal fluid (CSF) markers associated with C-IRIS before and during cART and clinical significance of CSF cryptococcal culture negativity pre-cART commencement. Of 106 patients commencing cART, 27 (25.5%) developed C-IRIS, 16 (15.1%) neurological deterioration-not C-IRIS, and 63 (59.4%) no neurological deterioration. On multivariable analysis, C-IRIS was associated with persistent CSF cryptococcal growth [hazard ratio (HR) 0.27, P=0.026] and lower CSF protein (HR 0.53, P=0.059) prior to cART and lower CD4 T-cell increases (HR 0.99, P=0.026) but not change in HIV viral load during cART. Using survival analysis, patients with a negative cryptococcal culture pre-cART commencement (n=51; 48.1%) experienced fewer episodes of neurological deterioration, C-IRIS, and cryptococcal relapse/persistence than patients with culture positivity (n=55; 51.9%, HR 0.33, 0.33, and 0.12 and P=0.0003, 0.0042, and 0.0004, respectively). Persistent CSF cryptococcal growth at cART initiation and poor CD4 T-cell increases on cART are strong predictors of C-IRIS. Approaches aimed at achieving CSF culture negativity prior to cART should be evaluated as a strategy to reduce rates of C-IRIS.