title: Improved kidney function in patients who switch their protease inhibitor from atazanavir or lopinavir to darunavir.
abstract: Atazanavir (ATV) and lopinavir (LPV) have been associated with kidney disease progression in HIV positive patients, with no data reported for darunavir (DRV). We examined kidney function in patients who switched their protease inhibitor from ATV or LPV to DRV.
  
  
  
  Cohort study.
  
  
  
  Data were from the UK CHIC study. We compared pre and post switch estimated glomerular filtration rate (eGFR) slopes (expressed in ml/min per 1.73 m per year) in all switchers and those with rapid eGFR decline (>5 ml/min per 1.73 m per year) on ATV or LPV. Mixed-effects models were adjusted for age, gender, ethnicity, eGFR at switch and time updated CD4 cell count, HIV RNA and cumulative tenofovir (tenofovir disoproxil fumarate) exposure.
  
  
  
  Data from 1430 patients were included. At the time of switching to DRV, median age was 45 years, 79% were men, 76% had an undetectable viral load, and median eGFR was 93 ml/min per 1.73 m. Adjusted mean (95% confidence interval) pre and post switch eGFR slopes were -0.84 (-1.31, -0.36) and 1.23 (0.80, 1.66) for ATV (P < 0.001), and -0.57 (-1.09, -0.05) and 0.62 (0.28, 0.96) for LPV (P < 0.001). Stable or improved renal function was observed in patients with rapid eGFR decline on ATV or LPV who switched to DRV [-15.27 (-19.35, -11.19) and 3.72 (1.78, 5.66), P < 0.001 for ATV, -11.93 (-14.60, -9.26) and 0.87 (-0.54, 2.27), P < 0.001 for LPV]. Similar results were obtained if participants who discontinued tenofovir disoproxil fumarate at the time of switch were excluded.
  
  
  
  We report improved kidney function in patients who switched from ATV or LPV to DRV, suggesting that DRV may have a more favourable renal safety profile.
authors.affiliation: aResearch Department of Infection and Population Health, University College LondonbChelsea and Westminster NHS Foundation Trust, LondoncSouth Tees Hospitals NHS Foundation Trust, MiddlesbroughdHIV I-Base, LondoneBrighton and Sussex University Hospitals, BrightonfKings College Hospital NHS Foundation Trust, London, UK.
authors.forename: Sophie
authors.initials: S
authors.lastname: Jose
authors.forename: Mark
authors.initials: M
authors.lastname: Nelson
authors.forename: Andrew
authors.initials: A
authors.lastname: Phillips
authors.forename: David
authors.initials: D
authors.lastname: Chadwick
authors.forename: Roy
authors.initials: R
authors.lastname: Trevelion
authors.forename: Rachael
authors.initials: R
authors.lastname: Jones
authors.forename: Deborah I
authors.initials: DI
authors.lastname: Williams
authors.forename: Lisa
authors.initials: L
authors.lastname: Hamzah
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Sabin
authors.forename: Frank A
authors.initials: FA
authors.lastname: Post
mesh_terms: D000328:Adult; D000069446:Atazanavir Sulfate / Q000008:administration & dosage / Q000009:adverse effects*; D015331:Cohort Studies; D065692:Cytochrome P-450 CYP3A Inhibitors; D000069454:Darunavir / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D005919:Glomerular Filtration Rate; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced* / Q000453:epidemiology*; D061466:Lopinavir / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D065692:Cytochrome P-450 CYP3A Inhibitors; D017320:HIV Protease Inhibitors; D061466:Lopinavir; D000069446:Atazanavir Sulfate; D000069454:Darunavir