681
Long-term Decay of HIV-1 Cellular Reservoir in HIV-1 Infected Childen Treated with Highly Active Antiretroviral Therapy
M Zanchetta1, S Walker2, N Burighel1, D Bellanova1, O Rampon3, C Giaquinto3, and Anita De Rossi*1
1AIDS Reference Ctr, Univ of Padova, Italy; 2Med Res Council, London, UK; and 3Univ of Padova, Italy
Background: Although HAART can control HIV-1
replication, a reservoir of infected cells persists despite prolonged
suppression of plasma
viremia. To investigate the decay of this reservoir,
we quantified HIV-1 DNA and HIV-1 mRNAs in peripheral blood mononuclear cells
(PBMC) of children on long-term HAART.
Methods: Fourteen children, who on HAART
achieved and maintained suppression of plasma viremia
(<50 copies/ml) for up to 48 months were studied. At baseline and at fixed
time points after HAART initiation, HIV-1 DNA, and HIV-1 unspliced
(RNAus) and multiply-spliced (RNAms)
mRNAs in PBMC
were analyzed with real-time PCR.
Results: At baseline, the median CD4+ T cell number was 219 (range
9-611) cells/μl, mean plasma HIV-1 RNA was 4.75 (SD 0.59) log10
copies/ml of plasma, and mean HIV-1 DNA was 2.85 (SD 0.66) log10 copies/106
cells. Intracellular HIV-1 RNAus and RNAms were detectable in 13 and 12 children, with a mean of
2.85 (SD 0.76) and 2.00 (SD 0.55) log10 copies/107 copies
GAPDH, respectively. At the end of the study, HIV-1 DNA was still detectable in
all but 2 children, and the mean HIV-1
DNA load was 1.76 (SD 0.56) log10 copies/106 cells. During
the first month of HAART, there were significant decreases in both plasma HIV-1
RNA and HIV-1 RNAms, yet HIV-1 RNAus
persisted in most of the children. HIV-1 DNA decay per 106 cells
during the first month of HAART was higher as greater was the concurrent rise
in CD4+ T cells (p=0.028), and was inversely correlated with
subsequent HIV-1 DNA decay (p=0.0012). Furthermore, rate of clearance of
HIV-1 DNA reservoir was accelerated from 1 to 9 months of HAART (median half-life 11 months) compared to the
following period (median half-life 69 months). Moreover, after 9 months of
therapy, the half-life of HIV-1 DNA decay was significantly longer in children
with detectable versus undetectable HIV-1 RNAus (p=
0.029).
Conclusions: These findings suggest that HIV-1
DNA decay in children is influenced by
increases in CD4+ T cells and by
residual viral replication. These
findings also indicate that the
total viral reservoir in chronically infected HAART-treated children
decays more slowly than
previously estimated in adults; this may
help in refining long-term treatment strategies
|
