title: Clonal analysis of HIV-1 variants in proviral DNA during treatment interruption in patients with multiple therapy failures.
abstract: BACKGROUND
  Treatment interruption (TI) in antiretroviral-treated patients on virological failure (VF) often results in a shift from resistant to wild-type HIV-1 in plasma. A clonal analysis was set out to determine the importance of archiving of resistant HIV-1 variants during TI and its relationship with the occurrence of a VF after treatment resumption.
  
  
  METHODS
  A fragment of the pol gene was cloned and sequenced from peripheral blood mononuclear cells DNA sampled at the end of TI. Clonal sequences were compared to bulk plasma sequences determined before TI, after TI and at VF.
  
  
  RESULTS
  Four patients were enrolled; all had a complete reversion to wild-type HIV-1 at the end of TI. In two patients with subsequent VF, archiving of minority resistant variants was detected in proviral DNA. Archived resistant variants were found to be phylogenetically linked to sequences detected before TI and at VF, suggesting the re-expansion of resistant HIV-1 from archived quasi-species.
  
  
  CONCLUSIONS
  In patients having a TI in the context of VF, archiving of resistant HIV-1 variants in proviral DNA can be involved into the mechanisms of further VF after treatment resumption.
authors.affiliation: Département de Virologie et Immunologie biologique, CHU de Bordeaux, Hôpital Pellegrin, Place Amélie Raba Léon, 33076 Bordeaux cedex, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Boucher
authors.forename: Patricia
authors.initials: P
authors.lastname: Recordon-Pinson
authors.forename: Didier
authors.initials: D
authors.lastname: Neau
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Ragnaud
authors.forename: Karine
authors.initials: K
authors.lastname: Titier
authors.forename: Muriel
authors.initials: M
authors.lastname: Faure
authors.forename: Hervé
authors.initials: H
authors.lastname: Fleury
authors.forename: Bernard
authors.initials: B
authors.lastname: Masquelier
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D004279:DNA, Viral / Q000235:genetics*; D024882:Drug Resistance, Viral; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D016333:HIV Protease / Q000235:genetics; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D009154:Mutation; D010802:Phylogeny; D011533:Proviruses / Q000235:genetics*; D017211:Treatment Failure; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D004279:DNA, Viral; D054303:HIV Reverse Transcriptase; D016333:HIV Protease