title: HIV-1 can persist in aged memory CD4+ T lymphocytes with minimal signs of evolution after 8.3 years of effective highly active antiretroviral therapy.
abstract: BACKGROUND
  Patients on long-term highly active antiretroviral therapy (HAART) were studied to determine persistence, drug resistance development, and evolution of HIV-1 proviral DNA.
  
  
  METHODS
  Peripheral blood mononuclear cells were obtained by large volume blood drawn (500 mL) from 8 clinically successfully treated patients who had received uninterrupted HAART for up to 8.9 years. HIV-1 load was determined by Taqman real-time polymerase chain reaction. Drug resistance mutations were determined by sequencing and ultrasensitive, allele-specific, reverse transcriptase (RT)-polymerase chain reaction.
  
  
  RESULTS
  HIV-1 DNA load was significantly higher in aged memory (CD45RO CD57) when compared with memory (CD45RO CD57) and naive (CD27 CD45RO) CD4 T cells after HAART. Sequencing revealed no major drug resistance mutations in protease in all patients and appearance of resistance mutations in RT in just 1 patient. In 1 of 5 patients with undetectable viremia during treatment, RT M184 substitutions were detected. Phylogenetic analysis showed short genetic distances between patient sequences.
  
  
  CONCLUSIONS
  During long-term HAART, HIV-1 is able to persist in terminally differentiated CD4 T cells as proviral DNA. Viral evolution was restricted, and in 80% of the patients with undetectable viremia, no sign of viral replication could be detected.
authors.affiliation: Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands. h.s.l.m.nottet@umcutrecht.nl
authors.forename: Hans S L M
authors.initials: HS
authors.lastname: Nottet
authors.forename: Sabine J
authors.initials: SJ
authors.lastname: van Dijk
authors.forename: Ewout B
authors.initials: EB
authors.lastname: Fanoy
authors.forename: Irma W
authors.initials: IW
authors.lastname: Goedegebuure
authors.forename: Dorien
authors.initials: D
authors.lastname: de Jong
authors.forename: Nienke
authors.initials: N
authors.lastname: Vrisekoop
authors.forename: Debbie
authors.initials: D
authors.lastname: van Baarle
authors.forename: Valerie
authors.initials: V
authors.lastname: Boltz
authors.forename: Sarah
authors.initials: S
authors.lastname: Palmer
authors.forename: Jan C C
authors.initials: JC
authors.lastname: Borleffs
authors.forename: Charles A B
authors.initials: CA
authors.lastname: Boucher
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000821:virology; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D016922:Cellular Senescence; D004279:DNA, Viral / Q000097:blood; D016333:HIV Protease / Q000235:genetics; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007156:Immunologic Memory; D009154:Mutation; D010802:Phylogeny; D013997:Time Factors
chemical_list: D004279:DNA, Viral; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; D016333:HIV Protease; C514803:p16 protease, Human immunodeficiency virus 1