The Effect of Rifampicin on Darunavir, Ritonavir, and Dolutegravir Exposure within Peripheral Blood Mononuclear Cells: a Dose Escalation Study.

ABSTRACT: Ritonavir-boosted darunavir (DRV/r) and dolutegravir (DTG) are affected by induction of metabolizing enzymes and efflux transporters caused by rifampicin (RIF). This complicates the treatment of people living with HIV (PLWH) diagnosed with tuberculosis. Recent data showed that doubling DRV/r dose did not compensate for this effect, and hepatic safety was unsatisfactory. We aimed to evaluate the pharmacokinetics of DRV, ritonavir (RTV), and DTG in the presence and absence of RIF in peripheral blood mononuclear cells (PBMCs). PLWH were enrolled in a dose-escalation crossover study with 6 treatment periods of 7 days. Participants started with DRV/r 800/100 mg once daily (QD), RIF and DTG were added before the RTV dose was doubled, and then they received DRV/r 800/100 twice daily (BD) and then

SUBMITTER: De Nicolo A 

PROVIDER: S-EPMC9211429 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature