title: Association of Gag cleavage sites to protease mutations and to virological response in HIV-1 treated patients.
abstract: OBJECTIVE
  The sequence variability in the protease and in the 5 Gag cleavage sites (CS) were explored to look for eventual associations between the mutations. Moreover, we have evaluated associations between the Gag region sequence and the virological response to Protease Inhibitors (PI).
  
  
  METHODS
  The protease and the 5 Gag CS sequences from 98 PI-experienced patients were sequenced and compared to the HXB2 reference sequence. Sixty patients, treated by Saquinavir plus Ritonavir, were studied to evaluate the clinical impact of the Gag region variability.
  
  
  RESULTS
  The relationship between 63 protease mutations and 21 Gag CS mutations were explored. Two patterns of mutations in the protease were identified: (M46I/L, I54V, V82A/T/F) was associated to the A431V and (K20I/R/M, L89M/I) to the S373Q and L449P. None of the Gag CS mutations resulting from PI treatment was associated to the virological response to SQV/r. On the other hand, the S373P mutation had a negative impact on the virological response that remained statistically significant in a multivariate analysis after adjustment on the number of PI resistance mutations.
  
  
  CONCLUSIONS
  These results evoke the pertinence to introduce some mutations found in the Gag CS in the algorithms used for the interpretation of resistance testing.
authors.affiliation: Laboratoire de Virologie (bâtiment CERVI), Hôpital Pitié-Salpêtrière, EA 2387, Université Pierre et Marie Curie (Paris 6), Paris, France. isabelle.malet@psl.aphp.fr <isabelle.malet@psl.aphp.fr>
authors.forename: Isabelle
authors.initials: I
authors.lastname: Malet
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Roquebert
authors.forename: Cécile
authors.initials: C
authors.lastname: Dalban
authors.forename: Marc
authors.initials: M
authors.lastname: Wirden
authors.forename: Bahia
authors.initials: B
authors.lastname: Amellal
authors.forename: Rachid
authors.initials: R
authors.lastname: Agher
authors.forename: Anne
authors.initials: A
authors.lastname: Simon
authors.forename: Christine
authors.initials: C
authors.lastname: Katlama
authors.forename: Dominique
authors.initials: D
authors.lastname: Costagliola
authors.forename: Vincent
authors.initials: V
authors.lastname: Calvez
authors.forename: Anne-Geneviève
authors.initials: AG
authors.lastname: Marcelin
mesh_terms: D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use; D001665:Binding Sites / Q000235:genetics; D024882:Drug Resistance, Viral; D015683:Gene Products, gag / Q000737:chemistry* / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D016333:HIV Protease / Q000235:genetics*; D017320:HIV Protease Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D019438:Ritonavir / Q000494:pharmacology / Q000627:therapeutic use; D019258:Saquinavir / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D019380:Anti-HIV Agents; D015683:Gene Products, gag; D017320:HIV Protease Inhibitors; D016333:HIV Protease; D019258:Saquinavir; D019438:Ritonavir