title: High prevalence of bevirimat resistance mutations in protease inhibitor-resistant HIV isolates.
abstract: OBJECTIVE
  Bevirimat is the first drug of a new class of antivirals that hamper the maturation of HIV. The objective of this study was to evaluate the sequence variability of the gag region targeted by bevirimat in HIV subtype-B isolates.
  
  
  METHODS
  Of 484 HIV subtype-B isolates, the gag region comprising amino acids 357-382 was sequenced. Of the patients included, 270 were treatment naive and 214 were treatment experienced. In the latter group, 48 HIV isolates harboured mutations associated with reverse transcriptase inhibitor resistance only, and 166 HIV isolates carried mutations associated with protease inhibitor resistance.
  
  
  RESULTS
  In the treatment-naive patient population, approximately 30% harboured an HIV isolate with at least one mutation associated with a reduced susceptibility to bevirimat (H358Y, L363M, Q369H, V370A/M/del and T371del). In HIV isolates with protease inhibitor resistance, the prevalence of bevirimat resistance mutations increased to 45%. Accumulation of mutations at four positions in the bevirimat target region, S368C, Q369H, V370A and S373P, was significantly observed. Mutations associated with bevirimat resistance were detected more frequently in HIV isolates with three or more protease inhibitor resistance mutations than in those with less than three protease inhibitor mutations.
  
  
  CONCLUSIONS
  Reduced bevirimat activity can be expected in one-third of treatment-naive HIV subtype-B isolates and significantly more in protease inhibitor-resistant HIV. These data indicate that screening for bevirimat resistance mutations before administration of the drug is essential.
authors.affiliation: Institute of Virology, University of Cologne, Cologne, Germany. jens.verheyen@uk-koeln.de
authors.forename: Jens
authors.initials: J
authors.lastname: Verheyen
authors.forename: Chris
authors.initials: C
authors.lastname: Verhofstede
authors.forename: Elena
authors.initials: E
authors.lastname: Knops
authors.forename: Linos
authors.initials: L
authors.lastname: Vandekerckhove
authors.forename: Axel
authors.initials: A
authors.lastname: Fun
authors.forename: Diede
authors.initials: D
authors.lastname: Brunen
authors.forename: Kenny
authors.initials: K
authors.lastname: Dauwe
authors.forename: Annemarie M J
authors.initials: AM
authors.lastname: Wensing
authors.forename: Herbert
authors.initials: H
authors.lastname: Pfister
authors.forename: Rolf
authors.initials: R
authors.lastname: Kaiser
authors.forename: Monique
authors.initials: M
authors.lastname: Nijhuis
mesh_terms: D024882:Drug Resistance, Viral / Q000187:drug effects* / Q000235:genetics; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D015995:Prevalence; D017422:Sequence Analysis, DNA; D013386:Succinates / Q000494:pharmacology*; D014315:Triterpenes / Q000494:pharmacology*; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000187:drug effects / Q000235:genetics*; D053978:Pentacyclic Triterpenes
chemical_list: D017320:HIV Protease Inhibitors; D013386:Succinates; D014315:Triterpenes; D054301:gag Gene Products, Human Immunodeficiency Virus; C479935:bevirimat; D053978:Pentacyclic Triterpenes