Abstract
BackgroundIn 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. Prolonged TB-IRIS has not been prospectively 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.MethodsWe pooled data from two prospective observational studies and a randomized controlled trial conducted in Cape Town, South Africa, that enrolled patients with paradoxical TB-IRIS. We used the same diagnostic approach and clinical case definitions for TB-IRIS in the 3 studies. Prolonged TB-IRIS was defined as TB-IRIS symptoms lasting > 90 days. Risk factors for prolonged TB-IRIS were analysed using Wilcoxon rank sum test, Fisher’s exact test, multivariate logistic regression and Cox proportional hazards models.ResultsTwo-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 (40.3 %) with adequate follow-up data, IRIS duration was > 90 days. Six patients (3.3 %), mainly with lymph node involvement, had IRIS duration > 1 year. In univariate logistic regression analysis the following were significantly associated with IRIS duration > 90 days: lymph node involvement at initial TB diagnosis, drug-resistant TB, lymph node TB-IRIS, and not being hospitalised at time of TB-IRIS diagnosis. In our multivariate logistic regression model lymph node TB-IRIS (aOR 2.27, 95 % CI 1.13–4.59) and not being hospitalised at time of TB-IRIS diagnosis (aOR for being hospitalised 0.5, 95 % CI 0.25-0.99) remained significantly associated with prolonged TB-IRIS, and drug-resistant TB was of borderline significance (aOR 3.26, 95 % CI 0.97–12.99). The association of not being hospitalised with longer duration of IRIS might be related to 1 of the 3 cohorts in which all patients were hospitalised at ART initiation with close inpatient follow-up. This could have resulted in diagnosis of milder cases and earlier IRIS treatment potentially resulting in shorter TB-IRIS duration in these hospitalised patients.ConclusionsAround 40 % of patients with TB-IRIS have symptoms for more than 90 days. Involvement of lymph nodes at time of TB-IRIS is an independent risk factor for prolonged TB-IRIS. Future studies should address whether more prompt anti-inflammatory treatment of lymph node TB-IRIS reduces the risk of prolonged TB-IRIS.Trial registrationThe randomized controlled trial was registered with Current Controlled Trials ISRCTN21322548 on 17 August 2005.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-016-1850-2) contains supplementary material, which is available to authorized users.
Highlights
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
We have previously described an overlap of tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) and rifampicin resistant TB [13] and for this reason when a patient with drug resistant TB was considered to have TB-IRIS they were not excluded from the analyses as we wished to determine if underlying drug resistant TB was a risk factor for prolonged TB-IRIS
Two-hundred and sixteen patients were diagnosed with paradoxical TB-IRIS across the three studies
Summary
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. Prolonged TB-IRIS has not been prospectively studied to date. Paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is an immunopathological reaction occurring in 4–54 % patients who start antiretroviral therapy (ART) while on treatment for tuberculosis (TB) [1,2,3]. TBIRIS causes substantial morbidity, necessitating hospitalisation and health care utilisation for diagnostic and therapeutic procedures [5, 6], when TB-IRIS has a protracted clinical course. The median duration of TB-IRIS symptoms reported from several observational studies and clinical trials has been 1–3 months [5,6,7,8,9,10,11]. Prolonged corticosteroid therapy in such patients may be associated with significant complications
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