1. Dynamics of total, linear nonintegrated, and integrated HIV-1 DNA in vivo and in vitro.
- Author
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Koelsch KK, Liu L, Haubrich R, May S, Havlir D, Günthard HF, Ignacio CC, Campos-Soto P, Little SJ, Shafer R, Robbins GK, D'Aquila RT, Kawano Y, Young K, Dao P, Spina CA, Richman DD, and Wong JK
- Subjects
- Acquired Immunodeficiency Syndrome drug therapy, Acquired Immunodeficiency Syndrome epidemiology, Acquired Immunodeficiency Syndrome immunology, Antiretroviral Therapy, Highly Active, California epidemiology, DNA, Viral blood, HIV Infections drug therapy, HIV Infections epidemiology, HIV Infections immunology, Humans, Kinetics, Viral Load, Acquired Immunodeficiency Syndrome genetics, CD4 Lymphocyte Count, DNA, Viral genetics, HIV Infections genetics, HIV-1 genetics, RNA, Viral blood, Virus Integration genetics
- 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)., 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.
- Published
- 2008
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