aDepartment of Infectious Diseases, Alfred Hospital and Monash University, Melbourne, Australia bDepartment of Infectious Diseases, King Edward VIII Hospital cHIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa dCentre for Virology, Burnet Institute, Melbourne, Australia eDepartment of Medical Microbiology, National Health Laboratory Services, Inkosi Albert Luthuli Central Hospital Academic Complex fDepartment of Microbiology and Infection Control, School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa gCentre for Population Health, Burnet Institute, Melbourne, Australia hCentre for the AIDS Programme of Research in South Africa, Doris Duke Medical Research Institute, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa iSchool of Pathology and Laboratory Medicine, University of Western Australia jDepartment of Clinical Immunology, Royal Perth Hospital and PathWest Laboratory Medicine, Perth, Australia.
AIDS. 2013 Aug 24;27(13):2089-99. doi: 10.1097/QAD.0b013e3283614a8d.
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.
接受抗反转录病毒治疗（cART）后，患有治疗后隐球菌性脑膜炎的 HIV 感染者存在进一步神经恶化的风险，主要是由于隐球菌病相关免疫重建炎症综合征（C-IRIS）。确定 C-IRIS 的预测因素可以进行风险分层。
24 周的前瞻性纵向队列研究。
南非德班。
130 名首次发生隐球菌性脑膜炎的 HIV 感染者
抗真菌治疗（两性霉素 B 1mg/kg 中位数 14 天，继以巩固和维持氟康唑）和 cART（从隐球菌性脑膜炎诊断中位数 18 天开始）。
在 cART 之前和期间与 C-IRIS 相关的临床、血液和脑脊液（CSF）标志物，以及 cART 前 CSF 隐球菌培养阴性的临床意义。
在 106 名开始 cART 的患者中，27 名（25.5%）发生 C-IRIS，16 名（15.1%）出现神经恶化-非 C-IRIS，63 名（59.4%）无神经恶化。多变量分析显示，cART 前持续的 CSF 隐球菌生长（危险比 [HR]0.27，P=0.026）和较低的 CSF 蛋白（HR0.53，P=0.059）与 C-IRIS 相关，而 cART 期间 CD4 T 细胞增加较少（HR0.99，P=0.026）。使用生存分析，cART 前隐球菌培养阴性的患者（n=51；48.1%）经历神经恶化、C-IRIS 和隐球菌复发/持续的次数少于培养阳性的患者（n=55；51.9%，HR0.33、0.33 和 0.12，P=0.0003、0.0042 和 0.0004）。
cART 开始时 CSF 中持续存在隐球菌生长和 cART 时 CD4 T 细胞增加不良是 C-IRIS 的强烈预测因素。应评估在 cART 前实现 CSF 培养阴性的方法，作为降低 C-IRIS 发生率的策略。
