title: Evolution of genotypic resistance to enfuvirtide in HIV-1 isolates from different group M subtypes.
abstract: BACKGROUND
  Enfuvirtide is active against isolates from different HIV-1 subtypes. In vitro and in vivo studies reveal that resistance mutations are primarily found within the region spanning amino acid 36-45 of gp41. However, most studies include only subtype B strains, while it is known that especially the env region is very divergent among subtypes.
  
  
  OBJECTIVE
  To analyze the gp41 HR1 genetic evolution during failure of enfuvirtide-containing salvage regimens in 19 HIV-1 patients infected with strains from different group M subtypes.
  
  
  METHODS
  The gp41 sequence was determined at baseline and upon failure in 19 patients. For a subset of 7 patients, samples were available after discontinuation of enfuvirtide.
  
  
  RESULTS
  Our results confirmed the conserved nature of the HR1 region. Escape mutants during chronic treatment with enfuvirtide were mainly observed within region 36-45. One novel mutation was identified, i.e. S42G in a subtype A1 strain.
  
  
  CONCLUSIONS
  Different subtypes escape enfuvirtide selective pressure through similar mutational patterns, however a new S42G variant was observed. The in vivo selection of S42G suggests that it might play a role in enfuvirtide resistance. Therefore, it could be considered as a candidate mutation to be included within drug resistance interpretation systems.
authors.affiliation: Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium. kris.covens@uz.kuleuven.ac.be
authors.forename: Kris
authors.initials: K
authors.lastname: Covens
authors.forename: Kabamba
authors.initials: K
authors.lastname: Kabeya
authors.forename: Yoeri
authors.initials: Y
authors.lastname: Schrooten
authors.forename: Nathalie
authors.initials: N
authors.lastname: Dekeersmaeker
authors.forename: Eric
authors.initials: E
authors.lastname: Van Wijngaerden
authors.forename: Anne-Mieke
authors.initials: AM
authors.lastname: Vandamme
authors.forename: Stéphane
authors.initials: S
authors.lastname: De Wit
authors.forename: Kristel
authors.initials: K
authors.lastname: Van Laethem
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D019380:Anti-HIV Agents / Q000494:pharmacology*; D024882:Drug Resistance, Viral; D000077560:Enfuvirtide; D019143:Evolution, Molecular; D015700:HIV Envelope Protein gp41 / Q000235:genetics* / Q000494:pharmacology*; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000145:classification / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010446:Peptide Fragments / Q000494:pharmacology*; D016879:Salvage Therapy / Q000379:methods; D017422:Sequence Analysis, DNA; D017211:Treatment Failure
chemical_list: D019380:Anti-HIV Agents; D015700:HIV Envelope Protein gp41; D010446:Peptide Fragments; C514787:gp41 protein, Human immunodeficiency virus 1; D000077560:Enfuvirtide