In:
Clinical Infectious Diseases, Oxford University Press (OUP), Vol. 70, No. 5 ( 2020-02-14), p. 859-866
Abstract:
The Early Pediatric Initiation Canada Child Cure Cohort (EPIC4) study is a prospective, multicenter, Canadian cohort study investigating human immunodeficiency virus–1 (HIV-1) reservoirs, chronic inflammation, and immune responses in children with perinatally acquired HIV-1 infection. The focus of this report is HIV-1 reservoirs and correlates in the peripheral blood of children who achieved sustained virologic suppression (SVS) for ≥5 years. Methods HIV-1 reservoirs were determined by measuring HIV-1 DNA in peripheral blood mononuclear cells and inducible cell-free HIV-1 RNA in CD4+ T-cells by a prostratin analogue stimulation assay. HIV serology was quantified by signal-to-cutoff ratio (S/CO). Results Of 228 enrolled participants, 69 achieved SVS for ≥5 years. HIV-1 DNA, inducible cell-free HIV-1 RNA, and S/COs correlated directly with the age of effective combination antiretroviral therapy (cART) initiation (P & lt; .001, P = .036, and P & lt; .001, respectively) and age when SVS was achieved (P = .002, P = .038, and P & lt; .001, respectively) and inversely with the proportion of life spent on effective cART (P & lt; .001, P = .01, and P & lt; .001, respectively) and proportion of life spent with SVS (P & lt; .001, P = .079, and P & lt; .001, respectively). Inducible cell-free HIV-1 RNA correlated with HIV-1 DNA, most particularly in children with SVS, without virologic blips, that was achieved with the first cART regimen initiated prior to 6 months of age (rho = 0.74; P = .037) or later (rho = 0.87; P & lt; .001). S/COs correlated with HIV-1 DNA (P = .003), but less so with inducible cell-free HIV-1 RNA (P = .09). Conclusions The prostratin analogue stimulation assay, with its lower blood volume requirement, could be a valuable method for evaluating inducible HIV-1 reservoirs in children. Standard commercial HIV serology may be a practical initial indirect measure of reservoir size in the peripheral blood of children with perinatally acquired HIV-1 infection.
Type of Medium:
Online Resource
ISSN:
1058-4838
,
1537-6591
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
2020
detail.hit.zdb_id:
2002229-3
