Dynamics of total, linear nonintegrated, and integrated HIV-1 DNA in vivo and in vitro
KK Koelsch, L Liu, R Haubrich, S May… - The Journal of …, 2008 - academic.oup.com
The Journal of infectious diseases, 2008•academic.oup.com
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 …
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 …
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 (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.
Oxford University Press