Longitudinal monitoring of 2-long terminal repeat circles in peripheral blood mononuclear cells from patients with chronic HIV-1 infection.
OBJECTIVE
To evaluate the potential use of 2-long terminal repeats (LTR) HIV circular DNA quantification for the monitoring of ongoing virus replication in treated HIV-1-infected patients.


METHODS
In a longitudinal setting, where the natural course of HIV-1 infection was in most cases disrupted by continuous or discontinuous antiviral therapy, 2-LTR circles of HIV-1 DNA were quantified in serial peripheral blood mononuclear cell samples, selected in retrospect from 16 patients with chronic HIV-1 infection, using quantitative real-time PCR. We compared variations of 2-LTR circle level with concomitant variations in plasma viral RNA level and with the frequency of productively infected cells and chromosome associated proviral DNA copy numbers in patient's peripheral blood mononuclear cells.


RESULTS
Antiviral treatment led to a sharp decrease in plasma viraemia and infectious cell frequency. In contrast, we found that levels of proviral DNA and 2-LTR circles were significantly lower under treatment only when groups of specimens that were homogeneous, with respect both to plasma viraemia and infectious cell frequency, were compared. Moreover, during the time of undetectable plasma viraemia, scarcely any decline in proviral DNA or 2-LTR circle levels was observed.


CONCLUSIONS
The low impact of antiviral treatment on 2-LTR circle levels in vivo, when plasma viraemia and infectious cell frequency both dramatically decline lead us to conclude that 2-LTR circles should not be used for the monitoring of recent viral replication in treated patients.
Brussel
Audrey
A
Département des Maladies Infectieuses, Institut Cochin, INSERM U567, CNRS UMR 8104, Université René Descartes, Paris, France.
Mathez
Dominique
D
Broche-Pierre
Sophie
S
Lancar
Rémi
R
Calvez
Thierry
T
Sonigo
Pierre
P
Leibowitch
Jacques
J
D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D002908:Chronic Disease; D004279:DNA, Viral / Q000097:blood; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D016325:HIV Long Terminal Repeat / Q000187:drug effects*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D008137:Longitudinal Studies; D008297:Male; D011533:Proviruses / Q000302:isolation & purification; D014766:Viremia / Q000188:drug therapy; D014779:Virus Replication / Q000187:drug effects
D019380:Anti-HIV Agents; D004279:DNA, Viral