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 Academic Article uri icon

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abstract

  • 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.

authors

  • Seigel, Sandra
  • Bitnun, Ari
  • Ransy, Doris G
  • Brophy, Jason
  • Kakkar, Fatima
  • Hawkes, Michael
  • Samson, Lindy
  • Annabi, Bayader
  • Pagliuzza, Amélie
  • Morand, Jacob-Adams
  • Sauve, Laura
  • Chomont, Nicolas
  • Lavoie, Stephanie
  • Kim, John
  • Sandstrom, Paul
  • Wender, Paul A
  • Lee, Terry
  • Singer, Joel
  • Read, Stanley E
  • Soudeyns, Hugo
  • Ariane, Alimenti
  • Petronela, Ancuta
  • Ari, Bitnun
  • Jason, Brophy
  • Jared, Bullard
  • Tae-Wook, Chun
  • Hélène, CF Côté
  • Joanne, Embree
  • Michael, T Hawkes
  • Fatima, Kakkar
  • Christos, Karatzios
  • Rupert, Kaul
  • John, Kim
  • Valérie, Lamarre
  • Normand, Lapointe
  • Pascal, Lavoie
  • Terry, Lee
  • Deborah, M Money
  • Dorothy, Moore
  • Stanley, Read
  • Robert, Reinhard
  • Lindy, Samson
  • Paul, Sandstorm
  • Laura, Sauve
  • Sandra, Seigel
  • Joel, Singer
  • Hugo, Soudeyns
  • Ben, Tan
  • Wendy, Vaudry

publication date

  • February 14, 2020