No increased risk of tuberculosis-related immune reconstitution inflammatory syndrome with integrase inhibitor-based antiretroviral therapy in people with HIV with profound immunosuppression.

INTRODUCTION: 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. METHODS: This was a retrospective review of 133 patients registered in the TB-HIV Registry of the Department of Health during the period 2014-2021. RESULTS: 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). CONCLUSION: 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.

T-Spot.TB outperforms tuberculin skin test in predicting development of active tuberculosis among household contacts.

BACKGROUND AND OBJECTIVE: In Hong Kong, neonatal Bacillus Calmette-Guerin (BCG) vaccination is practiced with 99% coverage. This study was to compare the performance of T-Spot.TB and tuberculin skin test (TST) in predicting tuberculosis (TB) among household contacts. METHODS: From 1 March 2006 to 31 July 2010, 1049 asymptomatic household contacts of smear-positive patients were simultaneously tested with T-Spot.TB and TST, and then followed for up to 5 years for development of TB. Attending clinicians and subjects were blinded to the results of T-Spot.TB. RESULTS: T-Spot.TB gave a significantly higher positive rate (32.7% vs 22.1%) and better association with exposure time than TST at the 15 mm cut-off. Agreement between T-Spot.TB and TST using cut-offs of 5, 10 and 15 mm were relatively poor (kappa 0.25-0.41) irrespective of presence or absence of BCG scar. Only T-Spot.TB positivity was negatively associated with BCG scar. Both T-Spot.TB (incidence rate ratio between test-positive and test-negative subjects, IRR: 8.2) and TST (IRR: 4.1, 6.1 and 2.8, using cut-offs of 5 mm, 10 mm and 15 mm, respectively) helped to predict TB. Using a TST cut-off of 15 mm, 56% of future TB cases and 62.5% of bacteriologically confirmed cases were missed. Lowering the TST cut-off to 10 mm or 5 mm could achieve sensitivity comparable with that of T-Spot.TB, but at the expense of lower specificities, with more positive tests (thus requiring treatment) per case of TB predicted. CONCLUSIONS: T-Spot.TB outperformed TST in predicting TB among household contacts in a high-income area with widespread BCG vaccination coverage.

Risk of active tuberculosis among schoolchildren in Hong Kong.

OBJECTIVE: To estimate the risk of active tuberculosis (TB) and its implication on preventive treatment among BCG-vaccinated schoolchildren. DESIGN: Cohort and case-control designs. SETTING: Community settings in a high-prevalence area. PARTICIPANTS: Children in primary school. The main exposure was their tuberculin response. MAIN OUTCOME MEASURES: Of 94,928 primary schoolchildren tuberculin tested during a routine school revaccination program in 1999, 656 with a tuberculin response at 20 mm or more were followed up prospectively through the territory-wide TB registry up to December 31, 2003, for the development of TB. In a separate case-control analysis, the tuberculin responses of children who subsequently had active TB (at the age of 10-15 years) were compared with those of their sex- and age-matched classmates to ascertain the relative risks of TB for different tuberculin reaction categories. The absolute and relative risks were applied to the 1999 cohort for estimating the incidence of TB among different tuberculin reactors. RESULTS: The annual incidence (95% confidence interval) of active TB was estimated to be 13.4 (5.6-40.6) per 100,000 for the entire cohort and 7.5 (2.4-24.5), 7.5 (1.7-32.0), 16.0 (4.4-57.2), 92.6 (26.6-320.2), and 340.6 (163.3-626.4) per 100,000 for children with a tuberculin reaction at 0 to 4, 5 to 9, 10 to 14, 15 to 19, and 20 mm or more, respectively. By using 10 mm as the cutoff, 482 (95% confidence interval, 163-1391) children have to be treated to prevent a single case of active TB within 5 years. Treatment will cover 17.5% of the cohort, but prevent only 54.1% of all active TB cases. CONCLUSION: It is desirable to reexamine the existing screening method for BCG-vaccinated children from high-prevalence countries.