Removal of Doravirine by Hemodialysis in HIV-Infected Patients With End-stage Renal Disease (ESRD)
Status:
Completed
Trial end date:
2021-06-14
Target enrollment:
Participant gender:
Summary
Doravirine is a novel non-nucleoside reverse transcriptase inhibitor that has demonstrated
good efficacy, tolerability, and safety for the treatment of patients with HIV infection in
phase III clinical trials. Doravirine achieved non- inferiority when compared with efavirenz-
and darunavir/ritonavir-based regimens. Doravirine is mainly metabolized and eliminated by
the liver, with only 6% of the drug being excreted unchanged through the urine.In a study
comparing 8 subjects with severe renal disease to 8 subjects without renal impairment, the
single dose exposure of doravirine was 43% higher in subjects with severe renal function
impairment.However, according to prescribing information, no dosage adjustment of doravirine
is required in patients with mild, moderate, or severe renal impairment. On the other hand,
data on doravirine pharmacokinetics in patients with ESRD on dialysis are lacking. This may
be of special interest because doravirine has a relatively low molecular weight and it is
only 76% bound to proteins in plasma. These characteristics could make possible for
hemodialysis to remove doravirine from plasma, potentially leading to subtherapeutic
concentrations of doravirine after the dialysis sessions. On the contrary, doravirine volume
of distribution is about 60 liters,15 what could limit extraction of doravirine by
hemodialysis. Since data on doravirine pharmacokinetics in PLWH with ESRD on dialysis are
lacking, our aim is to evaluate the effect of intermittent hemodialysis on doravirine
concentrations in HIV-infected patients with ESRD
Phase:
Phase 4
Details
Lead Sponsor:
Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia