Removal of Doravirine by Hemodialysis in HIV-Infected Patients With End-stage Renal Disease (ESRD)
Condition: HIV-infected Participants With ESRD Undergoing Routine Hemodialysis
MeSH terms: Kidney Failure, Chronic
Study type: Interventional
Phase: Phase 4

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
    

Detailed description: 
      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.
    

Intervention name(s): Doravirine
Intervention type(s): Drug
Intervention description(s): Participants will be told to take one tablet of doravirine (Pifeltro, MDS) once daily, with or without food, approximately at the day time that they usually finish the hemodialysis sessions. The rest of their antiretroviral regimen and concomitant medications will remain unchanged
Other intervention name(s): Pifeltro
Intervention model: Single Group Assignment
Intervention model description: This is a multi-centre, single-arm, open-label, pilot study in HIV-infected participants with ESRD undergoing routine hemodialysis.
All participants will receive doravirine 100 mg once daily during the study (5 days).
Masking: None (Open Label)
Primary purpose: Other
Keywords: HIV; ESRD; Doravirine