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

TitleDynamics of total, linear nonintegrated, and integrated HIV-1 DNA in vivo and in vitro.
Publication TypeJournal Article
Year of Publication2008
AuthorsKoelsch 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, Wong JK
JournalJ Infect Dis
Volume197
Issue3
Pagination411-9
Date Published2008 Feb 1
ISSN0022-1899
KeywordsAcquired Immunodeficiency Syndrome, Antiretroviral Therapy, Highly Active, California, CD4 Lymphocyte Count, DNA, Viral, HIV Infections, HIV-1, Humans, Kinetics, RNA, Viral, Viral Load, Virus Integration
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.

DOI10.1086/525283
Alternate JournalJ. Infect. Dis.
PubMed ID18248304
Grant ListAI027670 / AI / NIAID NIH HHS / United States
AI027763 / AI / NIAID NIH HHS / United States
AI029164 / AI / NIAID NIH HHS / United States
AI029193 / AI / NIAID NIH HHS / United States
AI034214 / AI / NIAID NIH HHS / United States
AI038858 / AI / NIAID NIH HHS / United States
AI043638 / AI / NIAID NIH HHS / United States
AI043752 / AI / NIAID NIH HHS / United States
AI047745 / AI / NIAID NIH HHS / United States
AI055388 / AI / NIAID NIH HHS / United States
AI060530 / AI / NIAID NIH HHS / United States
AI062435 / AI / NIAID NIH HHS / United States
NS051132 / NS / NINDS NIH HHS / United States