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Background: Early effective antiretroviral therapy (ART) limits circulating HIV-1 reservoirs, which is a goal for remission strategies. Our aim was to investigate the impact of early virological suppression (VS) on HIV-1 reservoir size in perinatally HIV-1-infected children with early ART initiation and more than six years of VS.
Methods: This study included 5 perinatally HIV-1 infected children ART-treated and followed up during sustained VS. Cell-associated HIV-1 DNA (CA-HIV-DNA) and two LTR (2-LTR) circles level were analyzed longitudinally: previous to ART initiation, at VS and throughout VS. Cell-associated unspliced HIV-1 RNA (CA-HIV-RNA) level was measured at last visit (after 6 years of VS). All these markers were quantified by semi-nested real time PCR. Antibody level was measured longitudinally (around 24 month of life, at VS and at last visit) using a commercial ELISA. All data were expressed as median (range).
Results: All infants received AZT as prophylaxis for 6 weeks, started ART and achieved VS at 4 (2-7) and 10 (8-11) months of life, respectively. Reservoir size, plasma viral load (pVL) and antibody measurements were illustrated per patient in Figure 1. CA-HIV-DNA showed a little decrease from ART initiation to last visit [time of VS 11 (6-16) yrs]: 4 (2.5-4.8) and 3 (0-3.6) log10 copies per million of peripheral blood mononuclear cells (cpm), respectively. The 2-LTR circles were detected in all, except one, patient at ART initiation [2.11 (0-2.4)], but it was undetectable in most cases throughout VS. Surprisingly, CA-HIV-RNA was detectable at last visit in all patients with a median of 3.6 (1.5-3.76) log10 copies per microgram of RNA. Finally, only one patient had absence of antibodies against HIV throughout the study, considered as a pediatric seroreversion case.
Conclusions: The size of circulating HIV reservoir in perinatally HIV-1 infected with more than 6 years of VS was still high for remission strategies. The high level of CA-HIV-RNA indicates viral activity despite sustained undetectable pVL. This work support the need for a very fast ART initiation, may be during the firsts hours of life, in order to limit significantly the reservoir size and HIV-1 potential replication.


Figure 1
[Figure 1]