Dolutegravir concentrations in children receiving 3-month weekly isoniazid and rifapentine (3HP) for tuberculosis prevention

In Tuberculosis Trials Consortium Study 35, which investigated the optimal dosing and safety of once-weekly isoniazid and rifapentine (3HP) in 69 children requiring tuberculosis preventive therapy, 7 children with HIV received 50 mg of once-daily dolutegravir. Plasma dolutegravir concentrations were consistent with those predicted in children on dolutegravir not receiving 3HP or potential metabolic inducers. All participants maintained viral suppression. Despite the expected induction effect of 3HP, results suggest that dolutegravir dose adjustments are not required.IMPORTANCEThis work describes the observed concentrations of dolutegravir in children co-administering rifapentine and dolutegravir. The work compares these concentrations with the model-simulated concentrations of a model developed using children not taking rifapentine or other metabolically inducing agents but who were administering dolutegravir. These data are the first available in children and are valuable in understanding the interaction of dolutegravir and rifapentine in children.CLINICAL TRIALSThis study is registered with the Tuberculosis Trials Consortium Study 35 as NCT03730181.