title: Longitudinal Genetic Characterization Reveals That Cell Proliferation Maintains a Persistent HIV Type 1 DNA Pool During Effective HIV Therapy.
abstract: BACKGROUND
  The stability of the human immunodeficiency virus type 1 (HIV-1) reservoir and the contribution of cellular proliferation to the maintenance of the reservoir during treatment are uncertain. Therefore, we conducted a longitudinal analysis of HIV-1 in T-cell subsets in different tissue compartments from subjects receiving effective antiretroviral therapy (ART).
  
  
  METHODS
  Using single-proviral sequencing, we isolated intracellular HIV-1 genomes derived from defined subsets of CD4(+) T cells from peripheral blood, gut-associated lymphoid tissue and lymph node tissue specimens from 8 subjects with virologic suppression during long-term ART at 2 time points (time points 1 and 2) separated by 7-9 months.
  
  
  RESULTS
  DNA integrant frequencies were stable over time (<4-fold difference) and highest in memory T cells. Phylogenetic analyses showed that subjects treated during chronic infection contained viral populations with up to 73% identical sequence expansions, only 3 of which were observed in specimens obtained before therapy. At time points 1 and 2, such clonally expanded populations were found predominantly in effector memory T cells from peripheral blood and lymph node tissue specimens.
  
  
  CONCLUSIONS
  Memory T cells maintained a relatively constant HIV-1 DNA integrant pool that was genetically stable during long-term effective ART. These integrants appear to be maintained by cellular proliferation and longevity of infected cells, rather than by ongoing viral replication.
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet Department of Clinical Microbiology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Susanne
authors.initials: S
authors.lastname: von Stockenstrom
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet.
authors.forename: Lina
authors.initials: L
authors.lastname: Odevall
authors.affiliation: Westmead Millennium Institute for Medical Research University of Sydney, Westmead, Australia.
authors.forename: Eunok
authors.initials: E
authors.lastname: Lee
authors.affiliation: Department of Medicine.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Sinclair
authors.affiliation: Department of Epidemiology and Biostatistics, University of California-San Francisco.
authors.forename: Peter
authors.initials: P
authors.lastname: Bacchetti
authors.affiliation: Department of Medicine.
authors.forename: Maudi
authors.initials: M
authors.lastname: Killian
authors.affiliation: Department of Medicine.
authors.forename: Lorrie
authors.initials: L
authors.lastname: Epling
authors.affiliation: Leidos Biomedical Research, INC, Frederick National Laboratory for Cancer Research.
authors.forename: Wei
authors.initials: W
authors.lastname: Shao
authors.affiliation: Department of Medicine.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Hoh
authors.affiliation: Department of Medicine.
authors.forename: Terence
authors.initials: T
authors.lastname: Ho
authors.affiliation: Department of Microbiology and Immunology, Rega Institute, KU Leuven-University of Leuven, Belgium.
authors.forename: Nuno R
authors.initials: NR
authors.lastname: Faria
authors.affiliation: Department of Microbiology and Immunology, Rega Institute, KU Leuven-University of Leuven, Belgium.
authors.forename: Philippe
authors.initials: P
authors.lastname: Lemey
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet Department of Clinical Microbiology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Jan
authors.initials: J
authors.lastname: Albert
authors.affiliation: Department of Medicine.
authors.forename: Peter
authors.initials: P
authors.lastname: Hunt
authors.affiliation: Department of Medicine.
authors.forename: Lisa
authors.initials: L
authors.lastname: Loeb
authors.affiliation: Department of Medicine.
authors.forename: Christopher
authors.initials: C
authors.lastname: Pilcher
authors.affiliation: Department of Medicine.
authors.forename: Lauren
authors.initials: L
authors.lastname: Poole
authors.affiliation: Department of Medicine.
authors.forename: Hiroyu
authors.initials: H
authors.lastname: Hatano
authors.affiliation: Department of Medicine.
authors.forename: Ma
authors.initials: M
authors.lastname: Somsouk
authors.affiliation: Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Douek
authors.affiliation: Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
authors.forename: Eli
authors.initials: E
authors.lastname: Boritz
authors.affiliation: Department of Medicine.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Deeks
authors.affiliation: Department of Medicine.
authors.forename: Frederick M
authors.initials: FM
authors.lastname: Hecht
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet Westmead Millennium Institute for Medical Research University of Sydney, Westmead, Australia.
authors.forename: Sarah
authors.initials: S
authors.lastname: Palmer
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use*; D049109:Cell Proliferation; D004279:DNA, Viral / Q000235:genetics* / Q000302:isolation & purification; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D008137:Longitudinal Studies; D008198:Lymph Nodes / Q000821:virology; D010802:Phylogeny; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000502:physiology / Q000821:virology*
chemical_list: D019380:Anti-HIV Agents; D004279:DNA, Viral
keywords: HIV-1 persistence; HIV-1 reservoir; memory T cells