O tratamento anti-retroviral baseado em inibidor da integrase não aumenta o risco de TB-IRIS em pessoas com HIV tratadas para tuberculose: resultados do estudo randomizado refletido TB2

Background: Antiretroviral therapy (ART) initiation in people living with HIV (PWHIV) treated for tuberculosis (TB) may be complicated due to the occurrence of tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS). Integrase inhibitors (INSTIs), by providing a faster HIV-RNA decline than efavirenz, could increase the risk for this complication. We sought to assess incidence and determinants of TB-IRIS in PWHIV with TB on raltegravir or efavirenz-based ART. Methods: We conducted a secondary analysis of the ANRS 12300 Reflate TB 2 multicenter, phase 3 trial, that randomized ART-naive PWHIV on standard TB treatment, to receive raltegravir or efavirenz-based ART. TB-IRIS was defined according to the International Network for the Study of HIV-associated IRIS (INSHI) criteria. Incidence rates (IR) were estimated by 100 persons-year (PY), stratified Kaplan-Meier curves (log-rank test) and cox regression models were used to assess determinants of TB-IRIS. Results: Of 460 trial participants, 453 participants from Brazil, Côte d'Ivoire, Mozambique and Vietnam were included in this analysis. Median age 35 years (IQR: 29-43), 40% female, 69% pulmonary TB only, median CD4 102 (IQR 38-239) cells/µL and median HIV RNA 5.5 (IQR 5.0-5.8) log10 copies/mL. Overall, 48 participants developed TB-IRIS (IR = 24.2/100 PY), 19 cases in the raltegravir arm and 29 in the efavirenz arm (log-rank test: p=0.123) (Figure). Factors associated with TB-IRIS were: CD4 count =100 cells/µL, HIV RNA =500,000 copies/mL, extra-pulmonary/disseminated TB (Table). Conclusions: INSTI-based ART did not increase TB-IRIS risk. Low CD4 counts, high HIV RNA and extrapulmonary/disseminated TB were risk factors for TB-IRIS.