Journal Article

Clinical Correlates of Human Immunodeficiency Virus–1 (HIV-1) DNA and Inducible HIV-1 RNA Reservoirs in Peripheral Blood in Children With Perinatally Acquired HIV-1 Infection With Sustained Virologic Suppression for at Least 5 Years

Kakkar, Fatima, Hawkes, Michael, Pagliuzza, Amélie, Lavoie, Stephanie, Annabi, Bayader, Kim, John, Sandstrom, Paul, Read, Stanley E., Bitnun, Ari, Chomont, Nicolas, Lee, Terry, Singer, Joel, Brophy, Jason, Soudeyns, Hugo, Wender, Paul A., Ransy, Doris G., Sauve, Laura, Samson, Lindy, Morand, Jacob-Adams

2020

Overview

Abstract Background 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 < .001, P = .036, and P < .001, respectively) and age when SVS was achieved (P = .002, P = .038, and P < .001, respectively) and inversely with the proportion of life spent on effective cART (P < .001, P = .01, and P < .001, respectively) and proportion of life spent with SVS (P < .001, P = .079, and P < .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 < .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. Human immunodeficiency virus–1 (HIV-1) reservoir sizes in peripheral blood—measured by HIV-1 DNA, inducible cell-free RNA, and quantitative serology—correlate with earlier initiation of and proportions of life spent on effective treatment and with virologic suppression.

• Publisher: Oxford University Press
• Subject: and Commentaries / ARTICLES AND COMMENTARIES / Canada / Child / Cohort Studies / HIV Infections - drug therapy / HIV-1 - genetics / Humans / Leukocytes, Mononuclear / Prospective Studies / RNA / Viral Load