title: Dynamics of gag-pol minority viral populations in naive HIV-1-infected patients failing protease inhibitor regimen.
abstract: OBJECTIVE
  Recently, we have reported the role of baseline gag cleavage site mutations on the virological outcome of a dual-boosted protease inhibitor regimen in antiretroviral-naive patients (2IP-ANRS 127 trial). The objective of this substudy was to characterize, in patients experiencing virological failure, from the 2IP-ANRS 127 trial, the viral quasispecies present at baseline and at virological failure in gag cleavage site, in gag-pol frameshift and in protease-coding region.
  
  
  METHODS
  In four patients, we analysed by clonal analysis the viral population in gag cleavage site (p17/p24, p24/p2, p2/p7, p7/p1, p1/p6(gag)), in p6(gag), in gag-pol frameshift [p1/transframe protein (TFP)/p6(pol)] and in protease-coding region.
  
  
  RESULTS
  Clonal analysis of protease-coding region failed to detect major as well as minor protease inhibitor resistance-associated mutations in all four patients. In one patient, a I15V-mutated variant increased from 13 to 100% between baseline and week 24. Clonal analysis of gag and gag-pol cleavage site showed an increase in specific viral populations in p2/p7 cleavage site between baseline and virological failure in three patients. Among them, we described in one patient, that the predominant population at virological failure harboured in p2/p7 and TFP/p6(pol)-specific genotypic profiles associated with duplication of the P(T)APP motif in p6(gag) and the I15V protease mutation on the same individual molecular clones.
  
  
  CONCLUSIONS
  We highlighted the emergence of minority viral populations in the p2/p7 cleavage site between baseline and virological failure. In addition, we showed the association of a specific protease mutation with gag and gag-pol cleavage site substitutions, suggesting their possible role in virological outcome.
authors: Laboratoire de Virologie, Assistance Publique-Hôpitaux de Paris Groupe hospitalier Bichat-Claude Bernard, HUPNVS, Univ Paris Diderot, Paris, France. lucile.larrouy@bch.aphp.fr
authors: Lucile
authors: L
authors: Larrouy
authors: Charlotte
authors: C
authors: Charpentier
authors: Roland
authors: R
authors: Landman
authors: Catherine
authors: C
authors: Capitant
authors: Corine
authors: C
authors: Chazallon
authors: Patrick
authors: P
authors: Yeni
authors: Gilles
authors: G
authors: Peytavin
authors: Florence
authors: F
authors: Damond
authors: Françoise
authors: F
authors: Brun-Vezinet
authors: Diane
authors: D
authors: Descamps
mesh_terms: D002999:Clone Cells; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage*; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D009154:Mutation; D016133:Polymerase Chain Reaction; D012367:RNA, Viral; D060888:Real-Time Polymerase Chain Reaction; D017211:Treatment Failure; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism
chemical_list: D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D054301:gag Gene Products, Human Immunodeficiency Virus