Dynamics of total, linear nonintegrated, and integrated HIV-1 DNA in vivo and in vitro

J Infect Dis. 2008 Feb 1;197(3):411-9. doi: 10.1086/525283.


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).

Conclusion: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acquired Immunodeficiency Syndrome / drug therapy
  • Acquired Immunodeficiency Syndrome / epidemiology
  • Acquired Immunodeficiency Syndrome / genetics*
  • Acquired Immunodeficiency Syndrome / immunology
  • Antiretroviral Therapy, Highly Active
  • CD4 Lymphocyte Count*
  • California / epidemiology
  • DNA, Viral / blood
  • DNA, Viral / genetics*
  • HIV Infections / drug therapy
  • HIV Infections / epidemiology
  • HIV Infections / genetics*
  • HIV Infections / immunology
  • HIV-1 / genetics*
  • Humans
  • Kinetics
  • RNA, Viral / blood*
  • Viral Load
  • Virus Integration / genetics*


  • DNA, Viral
  • RNA, Viral