title: Human immunodeficiency virus type-1 (HIV-1) continues to evolve in presence of broadly neutralizing antibodies more than ten years after infection.
abstract: BACKGROUND
  The evolution of HIV-1 and its immune escape to autologous neutralizing antibodies (Nabs) during the acute/early phases of infection have been analyzed in depth in many studies. In contrast, little is known about neither the long-term evolution of the virus in patients who developed broadly Nabs (bNabs) or the mechanism of escape in presence of these bNabs.
  
  
  RESULTS
  We have studied the viral population infecting a long term non progressor HIV-1 infected patient who had developed broadly neutralizing antibodies toward all tier 2/3 viruses (6 clades) tested, 9 years after infection, and was then followed up over 7 years. The autologous neutralization titers of the sequential sera toward env variants representative of the viral population significantly increased during the follow-up period. The most resistant pseudotyped virus was identified at the last visit suggesting that it represented a late emerging escape variant. We identified 5 amino acids substitutions that appeared associated with escape to broadly neutralizing antibodies. They were V319I/S, R/K355T, R/W429G, Q460E and G/T463E, in V3, C3 and V5 regions.
  
  
  CONCLUSIONS
  This study showed that HIV-1 may continue to evolve in presence of both broadly neutralizing antibodies and increasing autologous neutralizing activity more than 10 years post-infection.
authors.affiliation: Université François Rabelais, Inserm UMR 966, Tours, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Chaillon
authors.forename: Martine
authors.initials: M
authors.lastname: Braibant
authors.forename: Stéphane
authors.initials: S
authors.lastname: Hué
authors.forename: Samia
authors.initials: S
authors.lastname: Bencharif
authors.forename: David
authors.initials: D
authors.lastname: Enard
authors.forename: Alain
authors.initials: A
authors.lastname: Moreau
authors.forename: Assia
authors.initials: A
authors.lastname: Samri
authors.forename: Henri
authors.initials: H
authors.lastname: Agut
authors.forename: Francis
authors.initials: F
authors.lastname: Barin
mesh_terms: D000595:Amino Acid Sequence; D000704:Analysis of Variance; D057134:Antibodies, Neutralizing / Q000097:blood*; D001499:Bayes Theorem; D019143:Evolution, Molecular; D015699:HIV Envelope Protein gp120 / Q000235:genetics* / Q000276:immunology; D015658:HIV Infections / Q000097:blood / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology; D006801:Humans; D016013:Likelihood Functions; D008390:Markov Chains; D008957:Models, Genetic; D009010:Monte Carlo Method; D010802:Phylogeny; D012641:Selection, Genetic; D012680:Sensitivity and Specificity; D017422:Sequence Analysis, DNA; D017741:Survivors
chemical_list: D057134:Antibodies, Neutralizing; D015699:HIV Envelope Protein gp120; C514793:gp120 protein, Human immunodeficiency virus 1