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


CONCLUSIONS
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.
Koelsch
Kersten K
KK
University of California, San Diego, USA. k.koelsch@cfi.unsw.edu.au
Liu
Lin
L
Haubrich
Richard
R
May
Susanne
S
Havlir
Diane
D
Günthard
Huldrych F
HF
Ignacio
Caroline C
CC
Campos-Soto
Paula
P
Little
Susan J
SJ
Shafer
Robert
R
Robbins
Gregory K
GK
D'Aquila
Richard T
RT
Kawano
Yuji
Y
Young
Karen
K
Dao
Phillip
P
Spina
Celsa A
CA
Richman
Douglas D
DD
Wong
Joseph K
JK
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D002140:California / Q000453:epidemiology; D004279:DNA, Viral / Q000097:blood / Q000235:genetics*; D015658:HIV Infections / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D007700:Kinetics; D012367:RNA, Viral / Q000097:blood*; D019562:Viral Load; D016662:Virus Integration / Q000235:genetics*
D004279:DNA, Viral; D012367:RNA, Viral