title: Rapid emergence of enfuvirtide resistance in HIV-1-infected patients: results of a clonal analysis.
abstract: OBJECTIVE
  To study the dynamics of enfuvirtide (T-20) resistance development in HIV-1-infected subjects.
  
  
  METHODS
  Clonal analysis of gp41 sequences was performed on serial samples obtained from HIV-1-infected subjects with early virologic failure of T-20-based regimens.
  
  
  RESULTS
  Enfuvirtide resistance mutations at codons 36 to 45 in the first heptad repeat of gp41 emerged within 2 weeks in most subjects and were associated with the return of plasma HIV-1 RNA level toward baseline by weeks 4 to 8. Mutations at codons 36 (G36E, G36D, or G36S) and 38 (V38A, V38G, or V38M) were the most commonly detected resistance mutations at week 2. Mutations at codons 40 (Q40H) and 43 (N43D) were more prevalent at week 4 than at week 2 and seemed to emerge more slowly than mutations at codons 36 and 38.
  
  
  CONCLUSIONS
  The rapid emergence of mutations associated with T-20 resistance in the absence of a fully suppressive antiretroviral regimen demonstrates a low genetic barrier to resistance and underscores the importance of combining T-20 with other active drugs when constructing regimens for highly treatment-experienced patients.
authors.affiliation: Section of Retroviral Therapeutics, Brigham and Women's Hospital, and Division of AIDS, Harvard Medical School, Boston, MA, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Lu
authors.forename: Steven G
authors.initials: SG
authors.lastname: Deeks
authors.forename: Rebecca
authors.initials: R
authors.lastname: Hoh
authors.forename: George
authors.initials: G
authors.lastname: Beatty
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Kuritzkes
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Martin
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Kuritzkes
mesh_terms: D000595:Amino Acid Sequence; D003001:Cloning, Molecular; D017931:DNA Primers; D024882:Drug Resistance, Viral; D000077560:Enfuvirtide; D015700:HIV Envelope Protein gp41 / Q000187:drug effects / Q000235:genetics* / Q000627:therapeutic use; D023581:HIV Fusion Inhibitors / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D010446:Peptide Fragments / Q000627:therapeutic use*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; D010446:Peptide Fragments; D000077560:Enfuvirtide