title: Prevalence of darunavir resistance mutations in HIV-1-infected patients failing other protease inhibitors.
abstract: BACKGROUND
  To estimate to what extent darunavir might be effective in patients failing distinct protease inhibitors (PIs), the genotypic resistance scores recently reported for the drug were examined in a large clinical HIV-1 drug resistance database.
  
  
  METHODS
  All clinical specimens from HIV-infected patients failing PI-based regimens referred for drug resistance testing between 1999 and 2007 to a reference centre in Madrid were analysed. Darunavir-specific resistance mutations listed by the September 2006 IAS-USA panel update were considered.
  
  
  RESULTS
  A total of 1021 genotypes from patients failing lopinavir (39.2%), nelfinavir (28.1%), saquinavir (14.5%), indinavir (13.7%), atazanavir (6.6%), fosamprenavir (5.3%) and tipranavir (1.1%) were identified. The prevalence of major darunavir resistance mutations was I50V 2.1%, I54M 1.3%, L76V 2.7% and I84V 14.5%. For minor darunavir resistance mutations, the rates were V11I 3.3%, V32I 3.9%, L33F 11%, I47V 2.1%, I54L 2.3%, G73S 12.8% and L89V 2.4%. Overall, 6.7% (n = 68) of the genotypes had three or more darunavir resistance mutations, which corresponded to a mean total number of PI resistance mutations of 12.3 +/- 1.9. In the multivariate analysis, prior fosamprenavir failure, prior saquinavir failure, the total number of PI resistance mutations and the number of prior PIs used were all independently associated with having more darunavir resistance mutations.
  
  
  CONCLUSIONS
  The prevalence of darunavir resistance mutations is low in patients failing other PI-based regimens, although prior failure to amprenavir and saquinavir might produce more cross-resistance to darunavir. Thus, darunavir may be a good option for patients who have failed other PI-based regimens.
authors.affiliation: Department of Infectious Diseases, Hospital Carlos III, Madrid, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Poveda
authors.forename: Carmen
authors.initials: C
authors.lastname: de Mendoza
authors.forename: Luz
authors.initials: L
authors.lastname: Martin-Carbonero
authors.forename: Angélica
authors.initials: A
authors.lastname: Corral
authors.forename: Verónica
authors.initials: V
authors.lastname: Briz
authors.forename: Juan
authors.initials: J
authors.lastname: González-Lahoz
authors.forename: Vincent
authors.initials: V
authors.lastname: Soriano
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics; D000069454:Darunavir; D024882:Drug Resistance, Viral / Q000235:genetics*; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D017320:HIV Protease Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D015497:HIV-1 / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D009154:Mutation; D013030:Spain; D013449:Sulfonamides / Q000494:pharmacology*
chemical_list: D017320:HIV Protease Inhibitors; D013449:Sulfonamides; D000069454:Darunavir