title: Efavirenz plasma levels can predict treatment failure and central nervous system side effects in HIV-1-infected patients.
abstract: OBJECTIVE
  Limited information exists on the clinical usefulness of drug level monitoring for efavirenz, a once-daily non-nucleoside reverse transcriptase inhibitor (NNRTI). The aim of this study was to determine whether efavirenz plasma concentration monitoring could predict treatment failure and central nervous system (CNS) tolerability.
  
  
  METHODS
  Blood samples were obtained from 130 HIV-infected patients receiving efavirenz in combination with other antiretroviral agents for more than 3 months. Efavirenz plasma concentrations were measured by high-performance liquid chromatography. An evaluation of CNS side-effects was performed and the viral load, CD4 cell count and other clinical and laboratory data were assessed. In 85 patients, these measures were repeated at 3 month intervals.
  
  
  RESULTS
  Efavirenz plasma levels (n = 226) were measured at an average of 14 h after drug intake. Drug concentrations ranged from 125 to 15230 microg/l (median 2188). Large inter-patient (CV 118%) and limited intra-patient (CV 30%) variabilities were observed in efavirenz levels. Virological failure was observed in 50% of patients with low efavirenz levels (< 1000 microg/l) versus 22 and 18% in patients with 1000-4000 microg/l or more than 4000 microg/l, respectively. CNS toxicity was approximately three times more frequent in patients with high efavirenz levels (> 4000 microg/l) compared with patients with 1000-4000 microg/l.
  
  
  CONCLUSIONS
  Treatment failure and CNS side-effects are associated with low and high efavirenz plasma levels, respectively. The important inter-individual variability in efavirenz levels strongly argues for dose adjustment on the basis of therapeutic drug monitoring to optimize treatment.
authors.affiliation: Department of Medicine, University Hospital of Lausanne, Switzerland.
authors.forename: C
authors.initials: C
authors.lastname: Marzolini
authors.forename: A
authors.initials: A
authors.lastname: Telenti
authors.forename: L A
authors.initials: LA
authors.lastname: Decosterd
authors.forename: G
authors.initials: G
authors.lastname: Greub
authors.forename: J
authors.initials: J
authors.lastname: Biollaz
authors.forename: T
authors.initials: T
authors.lastname: Buclin
mesh_terms: D000328:Adult; D000368:Aged; D000480:Alkynes; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use; D048588:Benzoxazines; D002490:Central Nervous System / Q000187:drug effects*; D003521:Cyclopropanes; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D010078:Oxazines / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use; D011237:Predictive Value of Tests; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use; D017211:Treatment Failure; D019562:Viral Load
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D010078:Oxazines; D018894:Reverse Transcriptase Inhibitors; C098320:efavirenz