title: Prevalence of subtype-related polymorphisms associated with in vitro resistance to attachment inhibitor BMS-626529 in HIV-1 'non-B'-infected patients.
abstract: OBJECTIVE
  BMS-626529 is a member of the new drug class of HIV-1 attachment inhibitors currently in development. Mutations selected during in vitro experiments with BMS-626529 are located in the gp120 region: L116P, A204D, M426L, M434I-V506M and M475I. A differential antiviral activity of BMS-626529 was observed depending of the viral subtype. The aim of our study was to assess the prevalence of subtype-related polymorphisms previously described as being associated with in vitro resistance to BMS-626529 in patients infected with different HIV-1 'non-B' subtypes.
  
  
  METHODS
  The prevalence of substitutions in gp120 was assessed in 85 HIV-infected patients (not previously treated with attachment inhibitors and infected with HIV-1 'non-B' subtypes) by performing direct sequencing of the gp120 region.
  
  
  RESULTS
  The most prevalent HIV-1 subtype was CRF02_AG (n = 46, 54%). The M426L substitution was found in virus from 10 patients (11.8%), mainly in subtypes D and CRF02_AG. The M434I substitution was found in virus from 11 patients (12.9%), mainly in subtypes CRF02_AG and CRF06_cpx. None of the CRF02_AG viruses harboured both M426L and M434I substitutions.
  
  
  CONCLUSIONS
  In our series, the M426L substitution in the gp120 region was detected in 46% and 7% of subtype D and CRF02_AG samples, respectively, and might affect the activity of BMS-626529 against these specific subtypes. Further studies are needed to better describe associations between HIV-1 'non-B'-subtype-related polymorphism profiles and the level of phenotypic resistance to attachment inhibitor BMS-626529.
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Hôpital Bichat-Claude Bernard, Laboratoire de Virologie, and EA 4409 Paris-Diderot University, Paris 7, Paris, France. charlotte.charpentier@bch.aphp.fr
authors.forename: Charlotte
authors.initials: C
authors.lastname: Charpentier
authors.forename: Lucile
authors.initials: L
authors.lastname: Larrouy
authors.forename: Benoit
authors.initials: B
authors.lastname: Visseaux
authors.forename: Roland
authors.initials: R
authors.lastname: Landman
authors.forename: Marine
authors.initials: M
authors.lastname: Levittas
authors.forename: Alexandre
authors.initials: A
authors.lastname: Storto
authors.forename: Florence
authors.initials: F
authors.lastname: Damond
authors.forename: Yazdan
authors.initials: Y
authors.lastname: Yazdanpanah
authors.forename: Patrick
authors.initials: P
authors.lastname: Yeni
authors.forename: Françoise
authors.initials: F
authors.lastname: Brun-Vézinet
authors.forename: Diane
authors.initials: D
authors.lastname: Descamps
mesh_terms: D019943:Amino Acid Substitution; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000494:pharmacology*; D024882:Drug Resistance, Viral; D005838:Genotype; D015699:HIV Envelope Protein gp120 / Q000235:genetics*; D023581:HIV Fusion Inhibitors / Q000008:administration & dosage / 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; D020125:Mutation, Missense; D011110:Polymorphism, Genetic
chemical_list: D019380:Anti-HIV Agents; D015699:HIV Envelope Protein gp120; D023581:HIV Fusion Inhibitors; C514793:gp120 protein, Human immunodeficiency virus 1