title: Impact of Tacrolimus Compared With Cyclosporin on the Incidence of Acute Allograft Rejection in Human Immunodeficiency Virus-Positive Kidney Transplant Recipients.
abstract: BACKGROUND
  Kidney transplantation (KT) of human immunodeficiency virus (HIV)-positive patients has transformed the management of end-stage kidney disease in this population. Although favourable outcomes have been reported, patients experience high rates of acute allograft rejection (AR). We examined factors associated with AR in the first year after KT, with particular emphasis on the choice of calcineurin inhibitor (CNI) immunosuppressive therapy.
  
  
  METHODS
  We conducted a national observational cohort study of HIV/KT in the United Kingdom. Patients were included if HIV positive at KT, transplanted in the United Kingdom between January 2005 and December 2013, and did not experience primary graft failure. Kaplan-Meier methods were used to estimate host/graft survival and cumulative incidence of biopsy proven AR. Logrank tests were used to compare survival, and Cox proportional hazard models to examine factors associated with AR.
  
  
  RESULTS
  Our study analyzed the incidence of AR in the first year after KT in 78 HIV-positive patients of whom 31 initiated cyclosporin (CsA) and 47 tacrolimus (Tac) based immunosuppression. AR was observed in 28 patients (36%) after a median of 2.6 (interquartile range, 0.5-5.9) months. The cumulative incidence of AR at 1 year was 58% and 21% among patients on CsA and Tac, respectively (P =0.003). Choice of CNI was the only factor significantly associated with AR (hazard ratio for Tac vs CsA 0.25 [95% confidence interval, 0.11-0.57], P = 0.001). Subtherapeutic CNI concentrations were common in the first 12 weeks after KT.
  
  
  CONCLUSIONS
  Our data suggest that Tac may be the preferred CNI for use in KT in people living with HIV.
authors.affiliation: 1 Department of Renal Sciences, King's College London, London, United Kingdom. 2 Department of Renal Medicine, Royal Free London NHS Foundation Trust, London, United Kingdom. 3 Department of HIV Medicine and Infectious Diseases, Royal Free London NHS Foundation Trust, London, United Kingdom. 4 Department of Renal Medicine, Imperial College Healthcare NHS Trust, London, United Kingdom. 5 Department of HIV Medicine, Chelsea and Westminster Hospital, London, United Kingdom. 6 Department of Renal Medicine, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom. 7 Institute of Pharmaceutical Science, King's College London, London, United Kingdom. 8 Department of HIV Research, King's College Hospital NHS Foundation Trust, London, United Kingdom.
authors.forename: Esther
authors.initials: E
authors.lastname: Gathogo
authors.forename: Mark
authors.initials: M
authors.lastname: Harber
authors.forename: Sanjay
authors.initials: S
authors.lastname: Bhagani
authors.forename: Jeremy
authors.initials: J
authors.lastname: Levy
authors.forename: Rachael
authors.initials: R
authors.lastname: Jones
authors.forename: Rachel
authors.initials: R
authors.lastname: Hilton
authors.forename: Graham
authors.initials: G
authors.lastname: Davies
authors.forename: Frank A
authors.initials: FA
authors.lastname: Post
mesh_terms: D000208:Acute Disease; D000368:Aged; D064591:Allografts; D065095:Calcineurin Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D016572:Cyclosporine / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D006084:Graft Rejection / Q000175:diagnosis / Q000276:immunology / Q000401:mortality / Q000517:prevention & control*; D015658:HIV Infections / Q000175:diagnosis / Q000276:immunology / Q000401:mortality / Q000821:virology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015994:Incidence; D053208:Kaplan-Meier Estimate; D007676:Kidney Failure, Chronic / Q000175:diagnosis / Q000401:mortality / Q000601:surgery*; D016030:Kidney Transplantation / Q000009:adverse effects / Q000401:mortality; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D016559:Tacrolimus / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D016559:Tacrolimus