Prolonged tuberculosis-associated immune reconstitution inflammatory syndrome: characteristics and risk factors
Master Thesis
2015
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University of Cape Town
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Background: In a proportion of patients with HIV-associated tuberculosis who develop paradoxical immune reconstitution inflammatory syndrome (IRIS), the clinical course of IRIS is prolonged necessitating substantial health care utilization for diagnostic and therapeutic interventions. This phenomenon has not been systematically studied to date. We aimed to determine the proportion of patients with prolonged TB-IRIS, as well as the clinical characteristics and risk factors for prolonged TB-IRIS. Methods: We pooled data from two prospective observational studies and a randomized controlled trial that enrolled patients with paradoxical TB-IRIS using the same diagnostic approach and clinical case definitions in Cape Town, South Africa. Prolonged TB-IRIS was defined as TB-IRIS symptoms lasting > 90 days. Risk factors for TB-IRIS were analysed using Wilcoxon rank sum test, Fisher's exact test, multivariate logistic regression and Cox proportional hazards model. In a separate set of analyses, risk factors for relapsing after a 4-week course of prednisone for treatment of TB-IRIS were analysed. Results: Two-hundred and sixteen patients with TB-IRIS were included. The median duration of TB-IRIS symptoms was 71.0 days (IQR=41.0-113.2). In 73/181 patients with sufficient follow-up (40.3%) IRIS duration was > 90 days. Six patients (3.3%) had IRIS duration > 1 year, mainly with nodal involvement. In univariate logistic regression analysis, the following were significantly associated with IRIS duration > 90 days: lymph node involvement at initial TB diagnosis (p=0.02), drug-resistant TB (p=0.02), lymph node TB-IRIS (p=0.0005) and not being hospitalized at time of TB-IRIS diagnosis (p=0.004). The association with lymph node TB-IRIS (p=0.02) and hospitalization status (p=0.05) remained significant in the multivariate logistic regression model. In the Cox proportional hazards model, IRIS lymph node involvement was independently associated with lower hazards of IRIS resolution (HR 0.55, 95%CI=0.38-0.78). In univariate analysis those patients with lesser reductions in liver function abnormalities during prednisone treatment had a higher risk of relapse after stopping prednisone, but no significant associations remained in multivariate analysis. Conclusions: Around 40% of patients with TB-IRIS have symptoms for more than 90 days. Lymph node IRIS involvement is an independent risk factor for a prolonged course and in the small proportion of patients (3%) with symptoms more than one year this usually manifests with lymph node involvement. Whether earlier recognition and treatment of lymph node TB-IRIS could reduce the risk of prolonged TB-IRIS needs to be evaluated. Trial registration: The randomized controlled trial was registered with Current Controlled Trials ISRCTN21322548.
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Bana, T. 2015. Prolonged tuberculosis-associated immune reconstitution inflammatory syndrome: characteristics and risk factors. University of Cape Town.