title: Genetic barrier for attachment inhibitor BMS-626529 resistance in HIV-1 B and non-B subtypes.
abstract: OBJECTIVE
  The genetic barrier (defined as the number of genetic transitions/transversions needed to produce a resistance mutation) can differ between HIV-1 subtypes. The genetic barrier for the new attachment inhibitor BMS-626529 was evaluated in five HIV-1 subtypes.
  
  
  METHODS
  Nine substitutions associated with BMS-626529 resistance at seven amino acid positions (116, 204, 375, 426, 434, 475 and 506) were analysed in 300 nucleotide sequences of the env gene encoding the gp120 protein from antiretroviral-naive patients (60 for each subtype and recombinant: B, C, D, CRF01_AE and CRF02_AG).
  
  
  RESULTS
  Differently from the B subtype, some resistance mutations were found as natural polymorphisms in the C and D subtypes and the CRF02_AG and CRF01_AE recombinants for four positions of the env gene encoding the gp120 protein (375, 426, 434 and 475). The majority (five out of seven) of amino acid positions studied (116, 426, 434, 475 and 506) were relatively conserved (>63%) between the five HIV-1 subtypes, leading to a similar genetic barrier to mutations associated with resistance to BMS-626529. However, at positions 116 and 506 a minority of C and CRF02_AG subtypes had codons leading to a higher genetic barrier. Different predominant codons were observed at two out of seven positions (204 and 375) between the subtypes, with no effect on the calculated genetic barrier. However, for position 375, a minority of CRF02_AG sequences showed a lower genetic barrier to S375M/T resistance mutations.
  
  
  CONCLUSIONS
  In non-B HIV-1 subtypes, four out of seven studied positions presented mutations implicated in BMS-626529 resistance. Despite great variability of the HIV-1 envelope, there was no major impact of polymorphisms on the genetic barrier to acquisition of BMS-626529 resistance.
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, F-75013 Paris, France INSERM, UMR_S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, F-75013 Paris, France AP-HP, Hôpital Pitié-Salpêtrière, Service de Virologie, F-75013 Paris, France.
authors.forename: Djeneba B
authors.initials: DB
authors.lastname: Fofana
authors.affiliation: IAME, UMR 1137, Université Paris Diderot, Sorbonne Paris Cité, F-75018 Paris, France IAME, UMR 1137, INSERM, F-75018 Paris, France AP-HP, Hôpital Bichat-Claude Bernard, laboratoire de Virologie, F-75018 Paris, France.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Charpentier
authors.affiliation: Unité d'Epidémiologie Moléculaire de la Résistance du VIH, SEREFO-FMOS/FAPH, Université des Sciences Techniques et des Technologies, Bamako, Mali Service de Laboratoire, CHU Gabriel Toure, Université des Sciences Techniques et des Technologies, Bamako, Mali.
authors.forename: Almoustapha I
authors.initials: AI
authors.lastname: Maïga
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, F-75013 Paris, France INSERM, UMR_S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, F-75013 Paris, France AP-HP, Hôpital Pitié-Salpêtrière, Service de Virologie, F-75013 Paris, France.
authors.forename: Sidonie
authors.initials: S
authors.lastname: Lambert-Niclot
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, F-75013 Paris, France INSERM, UMR_S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, F-75013 Paris, France AP-HP, Hôpital Pitié-Salpêtrière, Service de Virologie, F-75013 Paris, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Sayon
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, F-75013 Paris, France INSERM, UMR_S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, F-75013 Paris, France AP-HP, Hôpital Pitié-Salpêtrière, Service de Virologie, F-75013 Paris, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Désiré
authors.affiliation: AP-HP, Hôpital Pitié-Salpêtrière, Service de médecine interne, F-75013 Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Simon
authors.affiliation: IAME, UMR 1137, Université Paris Diderot, Sorbonne Paris Cité, F-75018 Paris, France IAME, UMR 1137, INSERM, F-75018 Paris, France AP-HP, Hôpital Bichat-Claude Bernard, Service de maladies infectieuses, F-75018 Paris, France.
authors.forename: Yazdan
authors.initials: Y
authors.lastname: Yazdanpanah
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, F-75013 Paris, France INSERM, UMR_S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, F-75013 Paris, France AP-HP, Hôpital Pitié-Salpêtrière, Service de maladies infectieuses, F-75013 Paris, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Katlama
authors.affiliation: IAME, UMR 1137, Université Paris Diderot, Sorbonne Paris Cité, F-75018 Paris, France IAME, UMR 1137, INSERM, F-75018 Paris, France AP-HP, Hôpital Bichat-Claude Bernard, laboratoire de Virologie, F-75018 Paris, France.
authors.forename: Diane
authors.initials: D
authors.lastname: Descamps
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, F-75013 Paris, France INSERM, UMR_S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, F-75013 Paris, France AP-HP, Hôpital Pitié-Salpêtrière, Service de Virologie, F-75013 Paris, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Calvez
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, F-75013 Paris, France INSERM, UMR_S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, F-75013 Paris, France AP-HP, Hôpital Pitié-Salpêtrière, Service de Virologie, F-75013 Paris, France.
authors.forename: Anne-Geneviève
authors.initials: AG
authors.lastname: Marcelin
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, F-75013 Paris, France INSERM, UMR_S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, F-75013 Paris, France AP-HP, Hôpital Pitié-Salpêtrière, Service de Virologie, F-75013 Paris, France cathia.soulie@psl.aphp.fr.
authors.forename: Cathia
authors.initials: C
authors.lastname: Soulié
mesh_terms: D019943:Amino Acid Substitution; D024882:Drug Resistance, Viral; D005838:Genotype; D015699:HIV Envelope Protein gp120 / Q000235:genetics*; D023581:HIV Fusion Inhibitors / Q000494:pharmacology*; D015658:HIV Infections / Q000821:virology; D015497:HIV-1 / Q000145:classification / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D020125:Mutation, Missense; D010879:Piperazines / Q000494:pharmacology*; D011110:Polymorphism, Genetic; D014230:Triazoles / Q000494:pharmacology*
chemical_list: C584152:BMS-626529; D015699:HIV Envelope Protein gp120; D023581:HIV Fusion Inhibitors; D010879:Piperazines; D014230:Triazoles; C514793:gp120 protein, Human immunodeficiency virus 1
keywords: HIV; antiviral; drug resistance