Drugs suspected to be involved in the DDI
Dose adjustment performed
Feb. 10, 2019
Dose adjustment performed
Complete list of drugs taken by the patient
Darunavir (with Ritonavir or Cobicistat)
Complete list of all comedications taken by the patient, included that involved in the DDI
Quetiapine, folic acid, rosuvastatin, fenofibrate, trazodone, tibolone, flurazepam, delorazepam
Clinical case description
Liver function impairment
Patient is followed for psychiatric disorders (olygophrenie, depression/anxiety); HIV+ since 20 years, incomplete adherence in the past and several RAMs in the RT and PR genes. She was admitted to the ward for fever and bilateral otitis after having interrupted her ARVs (incomplete efficacy before and worsening neuropsychiatric symptoms with darunavir/cobicistat + maraviroc + dolutegravir). We re-started her antiretroviral therapy using darunavir/cobicistat (800/150 mg twice daily) plus etravirine (200 twice daily) and maraviroc (300 mg twice daily). She showed a good tolerability to the new regimen with no psychiatric or gastrointestinal complains. Quetiapine trough concentrations were in range (119 ng/mL, range 100-500) and she was discharged with no other modifications in her therapy.
No unwanted outcome
In this case a DRV/Cobi dose 800/150 mg every 12 hours was used, maybe to overcome PI resistance, for compliance reasons and taking into consideration the potential interaction between DRV/cobi and etravirine (see below). However, this is not the recommended dose of DRV/cobi, and this limits the generalization of this report. If DRV/cobi (instead of DRV/r) is to be used with etravirine, there is a potential DDI that could markedly decrease DRV concentrations (Moltó J et al. JAC 2018; 73:732-7) with potential risk of virological failure (However, that study was done with DRV/cobi once-daily, but not with DRV/cobi twice-daily). Quetiapine trough concentrations were within the normal range (although close to the lower margin). However, quetiapine daily doses in this patient were of 25 mg/daily, which are far below the usual dose (200-800 mg/daily). Although the European product label for quetiapine contraindicates the drug with CYP3A4 inhibitors (such as cobicistat), the US product label recommends reducing quetiapine to 1/6 of the original dose in that setting. However, the 25 mg daily dose used in this case is even lower than 1/6 of the lowest usual dose. Of note, a multidirectional DDI with quetiapine and ARV might be possible in this patient, as etravirine can act as a CYP3A4 inducer, potentially lowering quetiapine concentrations (and partially compensating the cobi inhibitory effect; quality of evidence: very low).