title: Impact of gag genetic determinants on virological outcome to boosted lopinavir-containing regimen in HIV-2-infected patients.
abstract: OBJECTIVE
  This study investigated the impact on virological outcome of the gag cleavage sites and the protease-coding region mutations in protease inhibitor-naive and protease inhibitor-experienced patients infected with HIV-2 receiving lopinavir (LPV) containing regimen.
  
  
  METHODS
  Baseline gag and protease-coding region were sequenced in 46 HIV-2 group A-infected patients receiving lopinavir. Virological response was defined as plasma viral load less than 100 copies/ml at month 3. Associations between virological response and frequencies of mutations in gag [matrix/capsid (CA), CA/p2, p2/nucleocapsid (NC), NC/p1, p1/p6] and gag-pol (NC/p6) cleavage site and protease-coding region, with respect to the HIV-2ROD strain, were tested using Fisher's exact test.
  
  
  RESULTS
  Virological response occurred in 14 of 17 (82%) protease inhibitor-naive and 17 of 29 (59%) protease inhibitor-experienced patients. Virological failure was associated with higher baseline viral load (median: 6765 versus 1098 copies/ml, P = 0.02). More protease-coding region mutations were observed in protease inhibitor-experienced compared with protease inhibitor-naive patients (median: 8 versus 5, P = 0.003). In protease inhibitor-naive patients, T435A (NC/p6), V447M (p1/p6), and Y14H (protease-coding region) were associated with virological failure (P = 0.011, P = 0.033, P = 0.022, respectively). T435A and V447M were associated with Y14H (P = 0.018, P = 0.039, respectively). In protease inhibitor-experienced patients, D427E (NC/p1) was associated with virological response (P = 0.014). A430V (NC/p1) and I82F (protease-coding region) were associated with virological failure (P = 0.046, P = 0.050, respectively). Mutations at position 430 were associated with a higher number of mutations in protease-coding region (median: 10 versus 7, P = 0.008).
  
  
  CONCLUSIONS
  We have demonstrated, for the first time, an association between gag, gag-pol cleavage site and protease-coding region mutations, with distinct profiles between protease inhibitor-naive and protease inhibitor-experienced patients. These mutations might impact the virological outcome of HIV-2-infected patients receiving LPV-containing regimen.
authors.affiliation: Laboratoire de Virologie, AP-HP Groupe Hospitalier Bichat-Claude Bernard, HUPNVS, Univ Paris Diderot, PRES Sorbonne Paris Cité, Paris, France. lucile.larrouy@bch.aphp.fr
authors.forename: Lucile
authors.initials: L
authors.lastname: Larrouy
authors.forename: Alexandre
authors.initials: A
authors.lastname: Vivot
authors.forename: Charlotte
authors.initials: C
authors.lastname: Charpentier
authors.forename: Antoine
authors.initials: A
authors.lastname: Bénard
authors.forename: Benoit
authors.initials: B
authors.lastname: Visseaux
authors.forename: Florence
authors.initials: F
authors.lastname: Damond
authors.forename: Sophie
authors.initials: S
authors.lastname: Matheron
authors.forename: Geneviève
authors.initials: G
authors.lastname: Chene
authors.forename: Françoise
authors.initials: F
authors.lastname: Brun-Vezinet
authors.forename: Diane
authors.initials: D
authors.lastname: Descamps
mesh_terms: D004279:DNA, Viral / Q000187:drug effects; D024882:Drug Resistance, Viral / Q000187:drug effects / Q000235:genetics; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics*; D016333:HIV Protease / Q000187:drug effects / Q000235:genetics; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D015498:HIV-2 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D061466:Lopinavir / Q000494:pharmacology*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D011480:Protease Inhibitors / Q000494:pharmacology*; D019562:Viral Load / Q000187:drug effects; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000187:drug effects / Q000235:genetics*; D054302:pol Gene Products, Human Immunodeficiency Virus / Q000187:drug effects / Q000235:genetics*
chemical_list: D004279:DNA, Viral; D017320:HIV Protease Inhibitors; D011480:Protease Inhibitors; D054301:gag Gene Products, Human Immunodeficiency Virus; D054302:pol Gene Products, Human Immunodeficiency Virus; D061466:Lopinavir; D016333:HIV Protease