A nomogram for predicting paradoxical immune reconstitution inflammatory syndrome associated with cryptococcal meningitis among HIV-infected individuals in China

Cryptococcal meningitis (CM) associated immune reconstitution inflammatory syndrome (CM-IRIS) is the second most common complication in HIV-infected individuals with cryptococcal meningitis, with a reported mortality rate ranging from 8 to 30%. Given the devastating consequences of CM-IRIS related intracranial neuroinflammation and its challenging in diagnosis, we conducted a study to explore the risk factors and the occurrence of paradoxical CM-IRIS in HIV-infected patients, which is of great value for prevention and clinical management.

We conducted a retrospective cohort study to identify the indicators associated with paradoxical CM-IRIS among 86 HIV-infected patients with CM using univariate and multivariate cox analysis. A nomogram was constructed using selected variables to evaluate the occurrence of paradoxical CM-IRIS at 6 months and 12 months after ART initiation. The discrimination and calibration of the nomogram were assessed by concordance index (C-index) and calibration plots. Decision curves analysis (DCA) were used to evaluate clinical effectiveness of the nomogram. Subsequently, to help clinicians recognize patients at high risk faster, patients were divided into high-risk and low-risk groups according to the best cutoff point identified by X-tile.

Of 86 AIDS patients with CM, 22.1% experienced paradoxical CM-IRIS at a median of 32 days after antiretroviral therapy (ART) initiation. The occurrence of paradoxical CM-IRIS was associated with age, ART initiation within 4 weeks of antifungal treatment, a four-fold increase in CD4 T cell counts, C-reactive protein levels, and hemoglobin levels independently. These five variables were further used to construct a predictive nomogram. The C-index (0.876) showed the favorable discriminative ability of the nomogram. The calibration plot revealed a high consistency between the predicted and actual observations. DCA showed that the nomogram was clinically useful. Risk stratification based on the total score of the nomogram showed well-differentiated in the high-risk and low-risk groups. Clinicians should pay attention to patients with total points high than 273.

We identified the predictive factors of paradoxical CM-IRIS and constructed a nomogram to evaluate the occurrence of paradoxical CM-IRIS in 6 months and 12 months. The nomogram represents satisfactory performance and might be applied clinically to the screening and management of high-risk patients.