title: The lymphocyte HIV reservoir in patients on long-term HAART is a memory of virus evolution.
abstract: OBJECTIVE
  To investigate the dynamics of the lymphocyte HIV reservoir in patients on prolonged and effective highly active antiretroviral therapy (HAART).
  
  
  METHODS
  Nine HAART-treated patients were selected on the basis of long-term infection and long-term undetectable plasma viral RNA. Five patients had received antiretroviral therapy before HAART. We compared a polymorphic region of the env gene (C2V4), and the part of the pol gene encoding the reverse transcriptase in pre-HAART plasma and in the reservoir lymphocytes during HAART; the first plasma sample taken after structured treatment interruption was also studied in three patients.
  
  
  METHODS
  Both regions of interest were amplified from plasma HIV RNA and cellular proviral DNA, then cloned, sequenced and subjected to phylogenetic analysis.
  
  
  RESULTS
  Diversity of the lymphocyte reservoir was found in six of nine patients. Archiving of pre-HAART plasma clones was observed in six of nine patients. 'Wild-type' and zidovudine-resistant strains co-existed in reservoir T cells of two pre-HAART treated patients. In three patients, no resistant virus was found in the T-cell reservoir despite the detection of resistant virus in pre-HAART plasmas. However, virus archiving was documented in two of these three patients on the basis of C2V4 analysis. Latently infected T cells only partly accounted for the plasma viral load rebound after structured treatment interruption.
  
  
  CONCLUSIONS
  The HIV lymphocyte reservoir is dynamic. Its diversity results mainly from successive archiving of circulating plasma viruses during the course of HIV infection. Archiving of resistant virus must be taken into account in therapeutic decisions.
authors.affiliation: INSERM E-109, Faculté de Médecine de Bicêtre, Université Paris XI, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Lambotte
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Chaix
authors.forename: Brigitte
authors.initials: B
authors.lastname: Gubler
authors.forename: Nadine
authors.initials: N
authors.lastname: Nasreddine
authors.forename: Christine
authors.initials: C
authors.lastname: Wallon
authors.forename: Cécile
authors.initials: C
authors.lastname: Goujard
authors.forename: Christine
authors.initials: C
authors.lastname: Rouzioux
authors.forename: Yassine
authors.initials: Y
authors.lastname: Taoufik
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Delfraissy
mesh_terms: D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D002908:Chronic Disease; D004197:Disease Reservoirs; D024882:Drug Resistance, Viral; D015752:Genes, env / Q000235:genetics; D015751:Genes, pol / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D010641:Phenotype; D012367:RNA, Viral / Q000235:genetics; D017423:Sequence Analysis, RNA; D014779:Virus Replication
chemical_list: D012367:RNA, Viral