title: Successful sofosbuvir-based therapy in HIV/hepatitis C virus coinfected liver transplant recipients with recurrent hepatitis C virus infection.
abstract: OBJECTIVE
  Recurrent hepatitis C virus (HCV) infection contributes to unfavourable outcomes in HIV/HCV coinfected liver transplant recipients. Direct-acting antiviral (DAA) therapies for HCV offer an opportunity to improve patient and allograft survival in this patient population. We evaluated treatment outcomes with sofosbuvir (SOF)-based DAA therapy among HIV/HCV coinfected liver transplant recipients.
  
  
  METHODS
  Single centre prospective cohort study.
  
  
  METHODS
  We identified eight HIV/HCV coinfected liver transplant recipients who were prospectively followed in the Northwestern University Viral Hepatitis Registry and who received SOF-based DAA therapy. We evaluated responses to therapy, including sustained HCV viral response 12 weeks after therapy completion (SVR12) and adverse effects.
  
  
  RESULTS
  Seven recipients (87.5%) completed 12 weeks of SOF-based therapy: SOF/simeprevir for genotype 1 (n = 6), SOF/ribavirin for genotype 2 (n = 1). Of persons who completed therapy, all achieved SVR12. Strategies for the management of expected and observed drug interactions consequent to the addition of simeprevir to preexisting complex medication regimens included modifications of HIV antiretroviral regimens (n = 4) and tacrolimus dosing (n = 4) and frequent monitoring of tacrolimus trough levels. Minor adverse effects were observed after DAA initiation. One episode of allograft rejection and one death occurred that were deemed unlikely related to HCV therapy.
  
  
  CONCLUSIONS
  High rates of HCV treatment success and no treatment-limiting adverse effects were observed in this HIV/HCV liver transplant cohort. Complex drug interactions were successfully managed in the context of multidisciplinary specialty care. Further studies are needed to assess the long-term effects of DAA therapy on patient and allograft survival among HIV/HCV coinfected liver transplant recipients.
authors.affiliation: aDivision of Infectious DiseasesbCenter for Global Health, Northwestern University Feinberg School of Medicine, ChicagocDepartment of Pharmacy, Northwestern Memorial Hospital, ChicagodDivision of Gastroenterology and Hepatology, Northwestern University Feinberg School of Medicine, ChicagoeDivision of Gastroenterology and Hepatology, University of Illinois Hospital and Health Sciences System, ChicagofDivision of Organ Transplantation and Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Grant
authors.forename: Claudia
authors.initials: C
authors.lastname: Hawkins
authors.forename: Hannah
authors.initials: H
authors.lastname: Brooks
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Palella
authors.forename: Sean W P
authors.initials: SW
authors.lastname: Koppe
authors.forename: Michael M
authors.initials: MM
authors.lastname: Abecassis
authors.forename: Valentina
authors.initials: V
authors.lastname: Stosor
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D060085:Coinfection / Q000188:drug therapy*; D064420:Drug-Related Side Effects and Adverse Reactions; D005500:Follow-Up Studies; D015658:HIV Infections / Q000150:complications*; D006526:Hepatitis C / Q000188:drug therapy*; D006801:Humans; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012008:Recurrence; D000069474:Sofosbuvir / Q000009:adverse effects / Q000627:therapeutic use*; D066027:Transplant Recipients; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D000069474:Sofosbuvir