title: Iatrogenic Cushing's syndrome due to drug interaction between glucocorticoids and the ritonavir or cobicistat containing HIV therapies.
abstract: Ritonavir and cobicistat, used as pharmacokinetic enhancers in combination with some antiretrovirals (ARVs) for the treatment of HIV, are potent inhibitors of the CYP3A4 isoenzyme. Most glucocorticoids are metabolised via the CYP3A4 pathway and iatrogenic Cushing's syndrome (ICS), with possible secondary adrenal insufficiency (SAI), is a recognised complication following co-administration with ritonavir or cobicistat. A structured approach for identifying and managing potentially affected individuals has not been established.We systematically identified patients with ICS/SAI and found substantial heterogeneity in clinical practice across three large London HIV centres. While this significant drug interaction and its complications are now well-recognised, it is apparent that there is no standardised approach to management or guidance for the general physician. Here we describe the management of ICS/SAI in our current practice, review the available evidence and suggest practice recommendations.
authors.affiliation: Chelsea and Westminster Hospital, London, UK emilieelliot@doctors.net.uk.
authors.forename: Emilie R
authors.initials: ER
authors.lastname: Elliot
authors.affiliation: University College London Hospitals Foundation Trust, London, UK.
authors.forename: Aikaterini
authors.initials: A
authors.lastname: Theodoraki
authors.affiliation: Mortimer Market Centre, London, UK.
authors.forename: Lakshmi R
authors.initials: LR
authors.lastname: Jain
authors.affiliation: Ian Charleson Centre for HIV Medicine, Royal Free London NHS Foundation Trust, London, UK.
authors.forename: Neal J
authors.initials: NJ
authors.lastname: Marshall
authors.affiliation: Chelsea and Westminster Hospital, London, UK.
authors.forename: Marta
authors.initials: M
authors.lastname: Boffito
authors.affiliation: University College London Hospitals Foundation Trust, London, UK.
authors.forename: Stephanie E
authors.initials: SE
authors.lastname: Baldeweg
authors.affiliation: Mortimer Market Centre, London, UK.
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Waters
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use; D000069547:Cobicistat / Q000009:adverse effects* / Q000627:therapeutic use; D003480:Cushing Syndrome / Q000139:chemically induced*; D004347:Drug Interactions; D005260:Female; D005938:Glucocorticoids / Q000009:adverse effects* / Q000627:therapeutic use; D015658:HIV Infections / Q000188:drug therapy; D006801:Humans; D007049:Iatrogenic Disease; D008297:Male; D008485:Medical Audit; D008875:Middle Aged; D012189:Retrospective Studies; D019438:Ritonavir / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D019380:Anti-HIV Agents; D005938:Glucocorticoids; D000069547:Cobicistat; D019438:Ritonavir
keywords: Adrenal insufficiency; Cushing’s syndrome; HIV; cobicistat; ritonavir