Dolutegravir can be safely administered to HIV-infected patients with advanced kidney disease (GRF <30 ml/min). However, little is known about dolutegravir removal by hemodialysis in patients with end-stage renal disease (ESRD). Our objective, therefore, was to evaluate the effect of hemodialysis on dolutegravir clearance in five anuric ESRD HIV-infected patients undergoing routine hemodialysis.
Exploratory clinical trial including 5 HIV-infected patients on stable antiretroviral treatment with ESRD undergoing routine hemodialysis. After enrolment (day 1), dolutegravir (Tivicay, Viiv) 50 mg once daily was added to antiretroviral treatment for five days. Blood samples were collected at the beginning and at the end of the dialysis session on day 5. Additionally, paired blood samples going into (predialyzer) and out (postdialyzer) of the dialyzer membrane, as well as a dialysate sample were collected during the dialysis session. Dolutegravir concentrations in plasma and in dialysate were determined by LC-MS/MS.
Five patients were included in the study. Two patients underwent conventional hemodialysis sessions while the three remaining underwent online hemodiafiltration (HDF-OL). Blood flows were held constant at 300 ml/min for patients on conventional hemodialysis, and at 400 ml/min for patients on HDF-OL. Dialysate flow was held constant at 500 ml/min for all participants. Dolutegravir concentrations in plasma and in dialysate are depicted in the table. Mean dolutegravir concentrations in plasma at the end of the dialysis session remained 30 fold above the protein binding-adjusted 90% inhibitory concentration.
Our results show minimal removal of dolutegravir by hemodialysis. Dolutegravir dosage adjustments seem, therefore, to be unnecessary in HIV-infected patients with ESRD undergoing hemodialysis.