title: The pharmacokinetics and pharmacogenomics of efavirenz and lopinavir/ritonavir in HIV-infected persons requiring hemodialysis.
abstract: OBJECTIVE
  To evaluate the pharmacokinetics and pharmacogenomics of efavirenz (EFV) and lopinavir/ritonavir (LPV/RTV) in HIV-infected persons requiring hemodialysis.
  
  
  METHODS
  Prospective, observational study of HIV-infected hemodialysis patients receiving one 600 mg tablet daily of EFV (N = 13) or three 133.3/33.3 mg capsules twice daily of LPV/RTV (N = 13).
  
  
  METHODS
  Twenty-four-hour EFV and 12-h LPV/RTV pharmacokinetics were assessed. Geometric mean ratios were calculated using historical controls with normal renal function. The effects of several candidate gene polymorphisms were also explored.
  
  
  RESULTS
  The geometric mean [95% confidence interval (CI); percentage of coefficient of variation (% CV)] Cmin, Cmax, and area under the curve (AUC) for the EFV group were 1.81 microg/ml (0.93, 3.53; 103%), 5.04 microg/ml (3.48, 7.29; 72%), and 71.5 microg h/ml (43.2, 118.3; 93%), respectively. These parameters were 2.76 microg/ml (1.86, 4.11; 53%), 8.45 microg/ml (6.41, 11.15; 52%), and 69.6 microg h/ml (55.6, 87.2; 37%) for LPV and 0.08 microg/ml (0.05, 0.14; 63%), 0.58 microg/ml (0.44, 0.76; 41%), and 3.74 microg h/ml (2.91, 4.80; 37%) for RTV. The AUC geometric mean ratios (90% CI) for EFV, LPV, and RTV were 132% (89, 197), 81% (67, 97), and 92% (76, 111), respectively. LPV Cmin was lower than expected in the hemodialysis group. Higher EFV concentrations were associated with the CYP2B6 516G>T polymorphism.
  
  
  CONCLUSIONS
  The pharmacokinetics of EFV and LPV/RTV in hemodialysis suggests that no dosing adjustments are necessary in treatment-naive patients. As HIV-infected hemodialysis patients are disproportionately black, the increased frequency of the CYP2B6 516G>T polymorphism may lead to higher EFV levels. The potentially lower LPV trough levels in this population suggest that LPV/RTV should be used with caution in protease-inhibitor-experienced patients.
authors.affiliation: Indiana University School of Medicine, Indianapolis, Indiana, USA. sgupta1@iupui.edu
authors.forename: Samir K
authors.initials: SK
authors.lastname: Gupta
authors.forename: Susan L
authors.initials: SL
authors.lastname: Rosenkranz
authors.forename: Yoninah S
authors.initials: YS
authors.lastname: Cramer
authors.forename: Susan L
authors.initials: SL
authors.lastname: Koletar
authors.forename: Lynda A
authors.initials: LA
authors.lastname: Szczech
authors.forename: Valerianna
authors.initials: V
authors.lastname: Amorosa
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Hall
mesh_terms: D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000097:blood*; D048588:Benzoxazines / Q000097:blood; D003521:Cyclopropanes; D004338:Drug Combinations; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000150:complications / Q000235:genetics; D017320:HIV Protease Inhibitors / Q000097:blood; D015497:HIV-1; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications; D061466:Lopinavir; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D011744:Pyrimidinones / Q000097:blood; D006435:Renal Dialysis; D018894:Reverse Transcriptase Inhibitors / Q000097:blood; D019438:Ritonavir / Q000097:blood
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D004338:Drug Combinations; D017320:HIV Protease Inhibitors; D011744:Pyrimidinones; D018894:Reverse Transcriptase Inhibitors; D061466:Lopinavir; C098320:efavirenz; D019438:Ritonavir
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