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Introduction Methods Results Conclusion The issue of whether integrase inhibitors (INSTIs) may confer a higher risk of paradoxical tuberculosis‐related immune reconstitution inflammatory syndrome (TB‐IRIS) compared with other classes of antiretroviral in people with HIV with a profound level of immunosuppression remains insufficiently explored. We aimed to assess whether such a higher risk exists by examining a cohort of patients with TB‐HIV initiating antiretroviral therapy (ART) in Hong Kong.This was a retrospective review of 133 patients registered in the TB‐HIV Registry of the Department of Health during the period 2014–2021.Sixteen of 70 patients (22.9%; 95% confidence interval [CI] 13.0–32.7) and 14 of 63 patients (22.2%; 95% CI 12.0–32.5) from the INSTI and non‐INSTI groups experienced TB‐IRIS (p = 0.920). The median intervals between ART initiation and IRIS among patients from the two groups were similar (3 weeks [interquartile range IQR 2.0–7.8] vs. 4 weeks [IQR 2.0–5.1], p = 0.620). The proportion of patients requiring steroid therapy were similar, as were the hospitalization rates. There was no IRIS‐related death in either group. The risk of TB‐IRIS with INSTI versus non‐INSTI was also similar in a stratified analysis in a subgroup of patients with a baseline CD4 count of <50 μL (10/33 [30.3%; 95% CI 14.6–46.0] vs. 10/22 [45.5%; 95% CI 24.7–66.3], p = 0.252) and another subgroup of patients with ART initiated within 4 weeks of anti‐TB treatment (10/26 [38.5%; 95% CI 19.8–57.2] vs. 10/23 [43.5%; 95% CI 23.2–63.7], p = 0.721).Our cohort study did not offer support for an increased risk of TB‐IRIS with INSTIs compared with non‐INSTIs, even in severely immunocompromised people with HIV. [ABSTRACT FROM AUTHOR]