title: Drug interactions between antiretrovirals and new or emerging direct-acting antivirals in HIV/hepatitis C virus coinfection.
abstract: OBJECTIVE
  We reviewed the pharmacokinetic interactions between direct-acting antivirals against hepatitis C virus (HCV) and antiretroviral agents.
  
  
  RESULTS
  Most relevant pharmacokinetic studies involve healthy individuals and refer to the already licensed HCV protease inhibitors, boceprevir and telaprevir. Data from a phase II clinical trial question the clinical relevance of the interactions between boceprevir and HIV protease inhibitors. The use of a higher dose of telaprevir appears to offset the effect of efavirenz on telaprevir metabolism according to another phase II trial. Boceprevir and particularly telaprevir substantially increase the exposure to maraviroc, similarly to other potent CYP3A4 inhibitors. Different dosages of faldaprevir and daclatasvir have been recommended to be used in combination with a boosted HIV protease inhibitor vs. an efavirenz-based antiretroviral regimen. HIV protease inhibitors appear to substantially increase the exposure to simeprevir. The interactions between sofosbuvir and most antiretroviral agents do not appear to be of clinical relevance or to require dosage modifications.
  
  
  CONCLUSIONS
  The drug-drug interaction studies for HCV direct-acting antivirals and antiretrovirals are important in determining the appropriate drug combinations and dosages. The clinical implications of these interactions need further assessment in different categories of patients, including those with cirrhosis.
authors.affiliation: aDepartment of Infectious Diseases/HIV Medicine, Royal Free London NHS Foundation Trust, London, UK bSt. James's Hospital, Dublin, Ireland cResearch Department of Infection, UCL, London dDepartment of Molecular & Clinical Pharmacology, University of Liverpool, Liverpool, UK *Dr Drosos E. Karageorgopoulos and Dr Omar El-Sherif contributed equally to the writing of this article.
authors.forename: Drosos E
authors.initials: DE
authors.lastname: Karageorgopoulos
authors.forename: Omar
authors.initials: O
authors.lastname: El-Sherif
authors.forename: Sanjay
authors.initials: S
authors.lastname: Bhagani
authors.forename: Saye H
authors.initials: SH
authors.lastname: Khoo
mesh_terms: D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D060085:Coinfection / Q000188:drug therapy; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy*; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D011480:Protease Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D044966:Anti-Retroviral Agents; D000998:Antiviral Agents; D011480:Protease Inhibitors