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

Ari Bitnun; Doris G Ransy; Jason Brophy; Fatima Kakkar; Michael Hawkes; Lindy Samson; Bayader Annabi; Amélie Pagliuzza; Jacob-Adams Morand; Laura Sauve; Nicolas Chomont; Stephanie Lavoie; John Kim; Paul Sandstrom; Paul A Wender; Terry Lee; Joel Singer; Stanley E Read; Hugo Soudeyns; Early Pediatric Initiation Canada Child Cure Cohort (EPIC4) Research Group

doi:10.1093/cid/ciz251

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

Clin Infect Dis. 2020 Feb 14;70(5):859-866. doi: 10.1093/cid/ciz251.

Authors

Ari Bitnun¹, Doris G Ransy², Jason Brophy³, Fatima Kakkar⁴, Michael Hawkes⁵, Lindy Samson³, Bayader Annabi^{2

6}, Amélie Pagliuzza⁷, Jacob-Adams Morand^{2

6}, Laura Sauve⁸, Nicolas Chomont^{6

7}, Stephanie Lavoie⁹, John Kim⁹, Paul Sandstrom⁹, Paul A Wender¹⁰, Terry Lee¹¹, Joel Singer^{11

12}, Stanley E Read¹, Hugo Soudeyns^{2

6}; Early Pediatric Initiation Canada Child Cure Cohort (EPIC4) Research Group

Collaborators

Early Pediatric Initiation Canada Child Cure Cohort (EPIC4) Research Group:
Alimenti Ariane, Ancuta Petronela, Bitnun Ari, Brophy Jason, Bullard Jared, Chun Tae-Wook, C F Côté Hélène, Embree Joanne, T Hawkes Michael, Kakkar Fatima, Karatzios Christos, Kaul Rupert, Kim John, Lamarre Valérie, Lapointe Normand, Lavoie Pascal, Lee Terry, M Money Deborah, Moore Dorothy, Read Stanley, Reinhard Robert, Samson Lindy, Sandstorm Paul, Sauve Laura, Seigel Sandra, Singer Joel, Soudeyns Hugo, Tan Ben, Vaudry Wendy

Affiliations

¹ Department of Pediatrics, Hospital for Sick Children, University of Toronto, Ontario.
² Centre de Recherche du Centre Hospitalier Universitaire (CHU) Sainte-Justine, Montreal, Quebec.
³ Department of Pediatrics, Children's Hospital of Eastern Ontario, University of Ottawa, Ontario.
⁴ Department of Pediatrics, CHU Sainte-Justine, Université de Montréal, Quebec.
⁵ Department of Pediatrics, Stollery Children's Hospital, University of Alberta, Edmonton.
⁶ Department of Microbiology, Infectiology & Immunology, Université de Montréal, Quebec.
⁷ Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Quebec.
⁸ Oak Tree Clinic, Women's Hospital and Health Centre of British Columbia, Department of Pediatrics, University of British Columbia, Vancouver.
⁹ National Human Immunodeficiency Virus (HIV) & Retrovirology Laboratories, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.
¹⁰ Department of Chemistry and Department of Chemical and Systems Biology, Stanford University, California.
¹¹ Canadian Institutes of Health Research Canadian HIV Trials Network, Vancouver, British Columbia.
¹² School of Population and Public Health, University of British Columbia, Vancouver, Canada.

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.

Keywords: HIV-1 DNA; child; inducible RNA; prostratin analogue; reservoir.

Publication types

Multicenter Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Canada
Child
Cohort Studies
HIV Infections* / drug therapy
HIV-1* / genetics
Humans
Leukocytes, Mononuclear
Prospective Studies
RNA
Viral Load

Substances

RNA

Abstract

Publication types

MeSH terms

Substances

Grants and funding