title: Drug-Drug Interactions With Antiviral Agents in People Who Inject Drugs Requiring Substitution Therapy.
abstract: OBJECTIVE
  To describe potential drug-drug interactions in the area of HIV/hepatitis C virus (HCV) coinfection and injection drug use, including those between antiretrovirals (ARVs), direct-acting antivirals (DAAs), and opioid-agonist therapy, and to supply a practical approach to their management.
  
  
  METHODS
  We searched PubMed for relevant articles published up until February 2015 as well as conference reports and drug-drug-interaction Web sites.
  
  
  METHODS
  We used the following search terms: pharmacokinetic and pharmacodynamic drug-drug interaction, opioid substitution, HIV, hepatitis and the individual names of the relevant agents of the following drug classes and the drug classes itself: reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors, protease inhibitors, direct-acting antivirals, opioide, benzodiazepines, anticonvulsants, antidepressants and antipsychotics. Additional references were identified from a review of literature citations and drug-drug interaction Web sites. In our evaluation, we included German- and English-language studies and reports addressing drug-drug interactions between opioid agonist therapy and ARVs or DAAs.
  
  
  RESULTS
  Pharmacokinetic data were available for all ARVs and DAAs except rilpivirine, indinavir, saquinavir, maraviroc, dolutegravir, and MK-8742 with buprenorphine as well as maraviroc with methadone Drug-drug interactions of potential clinical relevance are most likely to occur between opioid-replacement therapy and ARVs, particularly the nonnucleoside reverse transcriptase inhibitors, efavirenz and nevirapine, and HIV protease inhibitors.
  
  
  CONCLUSIONS
  Integrase inhibitors may be safely coadministered with opioid-replacement therapy. With respect to HCV DAAs, most currently approved and late-stage investigational agents do not have clinically significant interactions with opioid-replacement therapy. ARV and DAAs may interact with other drug classes commonly used in the opioid-dependent population, including benzodiazepines, antidepressants, anticonvulsants, and antipsychotics.
authors.affiliation: Interdisciplinary Expert Forum for HIV and Hepatitis Therapy (InXFo) GbR, Cologne, Germany lme@inxfo.de.
authors.forename: Leonie
authors.initials: L
authors.lastname: Meemken
authors.affiliation: German Association of Physicians in HIV Care, Berlin, Germany.
authors.forename: Nikola
authors.initials: N
authors.lastname: Hanhoff
authors.affiliation: University of Toronto, Canada.
authors.forename: Alice
authors.initials: A
authors.lastname: Tseng
authors.affiliation: Center for Interdisciplinary Medicine (CIM), Infectious Diseases, Münster, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Christensen
authors.affiliation: Herz-Jesu-Krankenhaus Hiltrup GmbH, Münster-Hitrup, Germany.
authors.forename: Anton
authors.initials: A
authors.lastname: Gillessen
mesh_terms: D000701:Analgesics, Opioid / Q000009:adverse effects / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D060085:Coinfection; D004347:Drug Interactions; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D006526:Hepatitis C / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D008691:Methadone / Q000009:adverse effects / Q000627:therapeutic use*; D058850:Opiate Substitution Treatment; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D015819:Substance Abuse, Intravenous / Q000150:complications / Q000188:drug therapy*
chemical_list: D000701:Analgesics, Opioid; D000998:Antiviral Agents; D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors; D008691:Methadone
keywords: HIV; antiretroviral therapy; direct-acting antivirals; drug-drug interaction; hepatitis; opioid substitution