Incidence and Predictors of Tuberculosis-associated IRIS in People With HIV Treated for Tuberculosis: Findings From Reflate TB2 Randomized Trial

• Published in: Open forum infectious diseases 2024-03, Vol.11 (3), p.ofae035-ofae035
• Main Authors: Coelho, Lara E, Chazallon, Corine, Laureillard, Didier, Escada, Rodrigo, N’takpe, Jean-Baptiste, Timana, Isabelle, Messou, Eugène, Eholie, Serge, Khosa, Celso, Chau, Giang D, Cardoso, Sandra Wagner, Veloso, Valdiléa G, Delaugerre, Constance, Molina, Jean-Michel, Grinsztejn, Beatriz, Marcy, Olivier, De Castro, Nathalie
• Format: Article
• Language: English
• Subjects: Clinical Trials and Therapeutics; Life Sciences; Santé publique et épidémiologie
• ISSN: 2328-8957; 2328-8957
• DOI: 10.1093/ofid/ofae035

Abstract Background After antiretroviral therapy (ART) initiation, people with HIV (PWH) treated for tuberculosis (TB) may develop TB-associated immune reconstitution inflammatory syndrome (TB-IRIS). Integrase inhibitors, by providing a faster HIV-RNA decline than efavirenz, might increase the risk for this complication. We sought to assess incidence and determinants of TB-IRIS in PWH with TB on raltegravir- or efavirenz-based ART. Methods We conducted a secondary analysis of the Reflate TB 2 trial, which randomized ART-naive PWH on standard TB treatment, to receive raltegravir- or efavirenz-based ART. The primary objective was to evaluate the incidence of TB-IRIS. Incidence rate ratio comparing TB-IRIS incidence in each arm was calculated. Kaplan-Meier curves were used to compare TB-IRIS–free survival probabilities by ART arm. Cox regression models were fitted to analyze baseline characteristics associated with TB-IRIS. Results Of 460 trial participants, 453 from Brazil, Côte d’Ivoire, Mozambique, and Vietnam were included in this analysis. Baseline characteristics were median age 35 years (interquartile range [IQR], 29–43), 40% female, 69% pulmonary TB only, median CD4, 102 (IQR, 38–239) cells/mm³, and median HIV RNA, 5.5 (IQR, 5.0–5.8) log copies/mL. Forty-eight participants developed TB-IRIS (incidence rate, 24.7/100 PY), 19 cases in the raltegravir arm and 29 in the efavirenz arm (incidence rate ratio 0.62, 95% confidence interval .35–1.10). Factors associated with TB-IRIS were: CD4 ≤ 100 cells/μL, HIV RNA ≥500 000 copies/mL, and extrapulmonary/disseminated TB. Conclusions We did not demonstrate that raltegravir-based ART increased the incidence of TB-IRIS compared with efavirenz-based ART. Low CD4 counts, high HIV RNA, and extrapulmonary/disseminated TB at ART initiation were associated with TB-IRIS. Integrase strand transfer inhibitor–based antiretroviral therapy (ART) did not increase the risk of tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) in the Reflate TB2 randomized controlled trial. Low CD4 counts and high HIV-RNA at ART initiation and extrapulmonary/disseminated TB were risk factors for TB-IRIS.