Impact of the time to achieve viral control on the dynamics of circulating HIV-1 reservoir in vertically infected children with long-term sustained virological suppression: A longitudinal study.

Autor: Moragas M; Laboratorio de BiologíaCelular y Retrovirus-CONICET, Hospital de Pediatría 'Prof. Dr. Juan P. Garrahan', Ciudad Autónoma de Buenos Aires, Argentina., Distefano M; Laboratorio de BiologíaCelular y Retrovirus-CONICET, Hospital de Pediatría 'Prof. Dr. Juan P. Garrahan', Ciudad Autónoma de Buenos Aires, Argentina., Mecikovsky D; Servicio de Epidemiología e Infectología, Hospital de Pediatría 'Prof. Dr. Juan P. Garrahan', Ciudad Autónoma de Buenos Aires, Argentina., Arazi Caillaud S; Servicio de Epidemiología e Infectología, Hospital de Pediatría 'Prof. Dr. Juan P. Garrahan', Ciudad Autónoma de Buenos Aires, Argentina., Cernadas C; DirecciónAsociada de Docencia e Investigación, Hospital de Pediatría 'Prof. Dr. Juan P. Garrahan', Ciudad Autónoma de Buenos Aires, Argentina., Bologna R; Servicio de Epidemiología e Infectología, Hospital de Pediatría 'Prof. Dr. Juan P. Garrahan', Ciudad Autónoma de Buenos Aires, Argentina., Aulicino P; Laboratorio de BiologíaCelular y Retrovirus-CONICET, Hospital de Pediatría 'Prof. Dr. Juan P. Garrahan', Ciudad Autónoma de Buenos Aires, Argentina., Mangano A; Laboratorio de BiologíaCelular y Retrovirus-CONICET, Hospital de Pediatría 'Prof. Dr. Juan P. Garrahan', Ciudad Autónoma de Buenos Aires, Argentina.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2018 Oct 23; Vol. 13 (10), pp. e0205579. Date of Electronic Publication: 2018 Oct 23 (Print Publication: 2018).
DOI: 10.1371/journal.pone.0205579
Abstrakt: Objective: Determine 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.
Methods: This 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.
Results: CA-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).
Conclusions: These 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.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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