The steady-state pharmacokinetics of fixed-dose combination dolutegravir+rilpivirine in hemodialysis.

Abstract

Objective: Fixed dose combination (FDC) dolutegravir (DTG) plus rilpivirine (RPV) is an approved antiretroviral treatment regimen for people with HIV. The steady-state pharmacokinetics of FDC DTG+RPV in hemodialysis has not been previously studied.

Design: We performed a single-center, prospective evaluation of the steady-state pharmacokinetics of FDC DTG +RPV in four adults without HIV either requiring hemodialysis and in four matched participants with normal renal function.

Methods: All participants received FDC DTG (50 mg)+RPV (25 mg) daily for 10-14 days with food before undergoing an intensive 24 h pharmacokinetic evaluation (performed between dialysis days for those requiring HD). Plasma drug and metabolite concentrations were measured using a validated UHPLC/MS/MS. Descriptive pharmacokinetic parameters were calculated.

Results: The hemodialysis and normal renal function participants (each group with two men and two women) were of similar ages (range, 50-60 years) and BMI (range, 18.5-34.5 kg/m 2 ). No participant experienced serious or grade 3-4 adverse events; there were no study discontinuations. The AUC 0 - τ mean (SD) ratios of hemodialysis to normal renal function for DTG and RPV were 1.1 (0.4) and 1.1 (0.9), respectively. The mean (SD) Cmin for DTG and RPV in the hemodialysis group were 1033 (252) and 49 (18) ng/ml, respectively.

Conclusion: Hemodialysis did not lead to clinically appreciable differential exposures to DTG and RPV. Exposures throughout the dosing interval were greater than the reported protein-binding-adjusted IC90 efficacy values for DTG (64 ng/ml) and RPV (12 ng/ml) in all participants. These data suggest no dosing modifications are needed for the FDC DTG+RPV regimen in hemodialysis.