title: Key drug-drug interactions with direct-acting antiviral in HIV-HCV coinfection.
abstract: OBJECTIVE
  We reviewed the most recent data on pharmacokinetic interactions between hepatitis C direct-acting antiviral (DAA) agents and HIV antiretrovirals (ARVs).
  
  
  RESULTS
  Drug interactions between DAAs and HIV ARVs are extrapolated from phase 1 drug-drug interaction (DDI) studies in healthy volunteers. Safety and efficacy data of DAA-ARV combinations are largely limited to the drug combinations permitted in phase 2 and 3 HIV-HCV coinfection trials. Paritapervir/ritonavir with ombitasvir and dasabuvir (3D) should not be coadministered with efavirenz, etravirine, elvitegravir/cobicistat or with additional doses of ritonavir. Atazanavir, darunavir and rilpivirine require cautious monitoring when used with 3D. The combination of sofosbuvir and ledipasvir can be safely used with most ARVs, but there is a risk of hyperbilirubinaemia with atazanavir. Tenofovir exposure is significantly increased when used with sofosbuvir-ledipasvir and a boosted protease inhibitor or emtricitabine/efavirenz, and therefore should be used with cautious monitoring for renal toxicity only when alternative therapy is not possible. Daclatasvir requires dosage modification with atazanavir, efavirenz and cobicistat. The coadministration of simeprevir with efavirenz, etravirine or ritonavir-boosted and cobicistat-boosted regimens is not recommended.
  
  
  CONCLUSIONS
  The safety and efficacy of HCV therapy in HIV-HCV coinfection is now comparable with HCV monoinfection, but drug interactions need to be carefully considered before instituting therapy to minimize potential harm. Real-world data are required to further assess the clinical implications of some DDIs.
authors.affiliation: aHepatology centre, St. James's Hospital, Dublin, Ireland bDepartment of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK cAssistance Publique-Hôpitaux de Marseille, Laboratoire de Pharmacocinétique et Toxicologie, Marseille, France dAix-Marseille University, Faculté de Pharmacie, INSERM UMR 911-CRO2, Marseille, France.
authors.forename: Omar
authors.initials: O
authors.lastname: El-Sherif
authors.forename: Saye
authors.initials: S
authors.lastname: Khoo
authors.forename: Caroline
authors.initials: C
authors.lastname: Solas
mesh_terms: D000998:Antiviral Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D060085:Coinfection / Q000188:drug therapy*; D004347:Drug Interactions; D004359:Drug Therapy, Combination / Q000009:adverse effects / Q000379:methods; D064420:Drug-Related Side Effects and Adverse Reactions; D015658:HIV Infections / Q000150:complications*; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents