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Effect of a 48-week Lopinavir/r Monotherapy on HIV1-DNA in Blood Cells in the MONARK Trial
Veronique Avettand-Fenoel*1, P Flandre2, M L Chaix1, J Ghosn3, C Delaugerre1, F Raffi4, P NgoVan5, I Cohen-Codar5, J F Delfraissy3, and C Rouzioux1
1Ctr Hosp Univ Necker, Univ Paris-Descartes, France; 2INSERM U720, Paris, France; 3Ctr Hosp Univ Bicetre, Le Kremlin-Bicetre, France; 4Ctr Hosp Univ Nantes, France; and 5Abbott France
Background: The effect of HAART regimen on HIV-1-infected blood
cells is estimated to be slightly lower than 1 log decrease after 1 year on
treatment. The effect of protease inhibitor (PI) monotherapy on the reservoirs
of HIV-1-infected cells is unknown and remains a concern. Our objective was to
investigate in the MONARK trial, the effect on the cellular HIV DNA reservoir
of a lopinavir/ritonavir (LPV/r) monotherapy compared to a triple therapy
including lopinavir (LPV)/r+zidovudine/lamivudine (AZT/3TC). By on-treatment
analysis, 56 of 67 (84%) patients in the LPV/r monotherapy arm had a plasma
viral load <50 copies /mL at week 48.
Methods: The MONARK trial randomized ARV-naïve
subjects with plasma viral load ≥100,000 copies/mL, and CD4+ T
cell count ≥100 cells/mm3 to receive either LPV/r monotherapy
or LPV/r-based triple combination. HIV DNA levels in blood cells were measured
both at baseline and week 48 in both arms. It was quantified in whole blood
samples, using the real time polymerase chain reaction (RT-PCR) HIV-1 DNA assay
of ANRS AC11; the cut-off value was at 6 copies/PCR.
Results: Overall, HIV-1 DNA samples were available
in 102 and 72 patients at baseline and week 48, respectively. Both arms were
balanced at baseline, with 4.26 and 4.21 log copies/million CD4+ T
cells in the monotherapy and triple-drug groups, respectively. A similar median
decrease was observed at week 48 in both arms: –0.75 log copies/million CD4+
T cells in the LPV/r arm vs –0.77 in the triple arm (p = 0.88). There
was no correlation between early HIV RNA decrease and HIV DNA decrease in both
groups. In the triple arm, the CD4+ T cell count increase was
associated to the HIV DNA decrease: a higher decrease of HIV DNA was associated
with a higher CD4+ T cell count increase (p = 0.057).
Conclusions: Our results show a very similar
effect of 48 weeks LPV/r monotherapy, vs a LPV/r-based triple regimen, on the
level of the HIV circulating reservoir expressed by HIV DNA level in blood
cells in naïve patients. These data suggest that, at the cellular level, this
LPV/r monotherapy regimen is potent, in comparison to a standard-of-care HAART.
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