title: Dynamics of total, linear nonintegrated, and integrated HIV-1 DNA in vivo and in vitro.
abstract: BACKGROUND
  In patients infected with human immunodeficiency virus type 1 (HIV-1), HIV-1 DNA persists during highly active antiretroviral treatment, reflecting long-lived cellular reservoirs of HIV-1. Recent studies report an association between HIV-1 DNA levels, disease progression, and treatment outcome. However, HIV-1 DNA exists as distinct molecular forms that are not distinguished by conventional assays.
  
  
  METHODS
  We analyzed HIV-1 RNA levels in plasma, CD4 cell counts, and levels of integrated and nonintegrated HIV-1 DNA in peripheral blood mononuclear cells (PBMCs) from patients with early or chronic infection before and during antiretroviral treatment. We also studied HIV-1 DNA decay in primary CD4 T cells infected in vitro. HIV-1 DNA was analyzed using an assay that is unaffected by the location of HIV-1 integration sites.
  
  
  RESULTS
  HIV-1 RNA levels and total HIV-1 DNA levels decayed rapidly in patients during receipt of suppressive antiretroviral therapy. Ratios of total HIV-1 DNA levels to integrated HIV-1 DNA levels were high before initiation of therapy but diminished during therapy. Levels of linear nonintegrated HIV-1 DNA decayed rapidly in vitro (t (1/2) = 1- 4.8 days).
  
  
  CONCLUSIONS
  Total HIV-1 DNA decays rapidly with suppression of virus replication in vivo. Clearance of HIV-1 DNA during the first 6 months of therapy reflects a disproportionate loss of nonintegrated HIV-1 DNA genomes, suggesting that levels of total HIV-1 DNA in PBMCs after prolonged virus suppression largely represent integrated HIV-1 genomes.
authors.affiliation: University of California, San Diego, USA. k.koelsch@cfi.unsw.edu.au
authors.forename: Kersten K
authors.initials: KK
authors.lastname: Koelsch
authors.forename: Lin
authors.initials: L
authors.lastname: Liu
authors.forename: Richard
authors.initials: R
authors.lastname: Haubrich
authors.forename: Susanne
authors.initials: S
authors.lastname: May
authors.forename: Diane
authors.initials: D
authors.lastname: Havlir
authors.forename: Huldrych F
authors.initials: HF
authors.lastname: Günthard
authors.forename: Caroline C
authors.initials: CC
authors.lastname: Ignacio
authors.forename: Paula
authors.initials: P
authors.lastname: Campos-Soto
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Little
authors.forename: Robert
authors.initials: R
authors.lastname: Shafer
authors.forename: Gregory K
authors.initials: GK
authors.lastname: Robbins
authors.forename: Richard T
authors.initials: RT
authors.lastname: D'Aquila
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kawano
authors.forename: Karen
authors.initials: K
authors.lastname: Young
authors.forename: Phillip
authors.initials: P
authors.lastname: Dao
authors.forename: Celsa A
authors.initials: CA
authors.lastname: Spina
authors.forename: Douglas D
authors.initials: DD
authors.lastname: Richman
authors.forename: Joseph K
authors.initials: JK
authors.lastname: Wong
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D002140:California / Q000453:epidemiology; D004279:DNA, Viral / Q000097:blood / Q000235:genetics*; D015658:HIV Infections / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D007700:Kinetics; D012367:RNA, Viral / Q000097:blood*; D019562:Viral Load; D016662:Virus Integration / Q000235:genetics*
chemical_list: D004279:DNA, Viral; D012367:RNA, Viral