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

Kersten K. Koelsch*, Lin Liu, Richard Haubrich, Susanne May, Diane Havlir, Huldrych F. Günthard, Caroline C. Ignacio, Paula Campos-Soto, Susan J. Little, Robert Shafer, Gregory K. Robbins, Richard T. D'Aquila, Yuji Kawano, Karen Young, Phillip Dao, Celsa A. Spina, Douglas D. Richman, Joseph K. Wong

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

120 Scopus citations

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-1DNA 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-1DNA 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 (t1/2 = 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.

Original languageEnglish (US)
Pages (from-to)411-419
Number of pages9
JournalJournal of Infectious Diseases
Volume197
Issue number3
DOIs
StatePublished - Feb 1 2008

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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