Abstract
ObjectiveDetermine the decay rate of HIV-1 DNA reservoir in vertically infected children during sustained viral suppression (VS) and how it is affected by the age at VS.MethodsThis study included 37 HIV-1 vertically infected children on suppressive antiretroviral therapy for at least 4 years. Children were grouped according to the age of antiretroviral therapy initiation (≤0.5 or >0.5 yrs) and to the age at VS (≤1.5, between >1.5 and 4, and >4 years). Decay of cell-associated HIV-1 DNA (CA-HIV-DNA) level and 2-long terminal repeats (2-LTR) circles frequency were analyzed over 4 years of viral suppression using piecewise linear mixed-effects model with two splines and logistic regression, respectively.ResultsCA-HIV-DNA in peripheral blood mononuclear cells had a significant decay during the first two years of VS [-0.26 (95% CI: -0.43, -0.09) log10 copies per one million cells (cpm)/year], and subsequently reached a plateau [-0.06 (95% CI: -0.15, 0.55) log10 cpm/year]. The initial decay was higher in children who achieved VS by 1.5 years of age compared to those who achieved VS between >1.5 and 4 years and those after 4 years of age: -0.51 (95% CI:-0.94, -0.07), -0.35 (95% CI:-0.83, 0.14), and -0.21 (95% CI:-0.39, -0.02) log10cpm PBMC/year, respectively. The 2-LTR circles frequency decayed significantly, from 82.9% at pre-VS to 37.5% and 28.1% at 2 and 4 years of VS, respectively (P = .0009).ConclusionsThese data highlight that achieving VS during the first 18 months of life limit the establishment of HIV-1 reservoirs, reinforcing the clinical benefit of very early effective therapy in children.
Highlights
Antiretroviral therapy (ART) allows sustained viral suppression (VS) in blood plasma, the ability to eradicate human immunodeficiency virus type 1 (HIV-1) has not been yet achieved
CA-HIV-DNA in peripheral blood mononuclear cells had a significant decay during the first two years of VS [-0.26 log10 copies per one million cells/year], and subsequently reached a plateau [-0.06 log10 cpm/year]
The initial decay was higher in children who achieved VS by 1.5 years of age compared to those who achieved VS between >1.5 and 4 years and those after 4 years of age: -0.51, -0.35, and -0.21 log10cpm peripheral blood mononuclear cell (PBMC)/year, respectively
Summary
Antiretroviral therapy (ART) allows sustained viral suppression (VS) in blood plasma, the ability to eradicate human immunodeficiency virus type 1 (HIV-1) has not been yet achieved. Simplified ART regimens, including break periods or interruption schedules, are being studied in order to improve treatment adherence and reduce the toxic effects associated with the drugs [14,15] These new therapeutic approaches that include HIV-1 infected patients with low to undetectable plasma viral load (pVL) require ongoing monitoring of the HIV1 reservoir size. CA-HIV-DNA may remain detectable despite sustained undetectable pVL; its level of decay might be of interest when assessing the long-term efficacy of ART on reservoirs It is not well defined how the time to achieve sustained VS, in those infants who controlled virus replication at chronic stage of infection, impacts on the size of the HIV-1 reservoir
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