| Title: |
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 |
| Authors: |
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, C F 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 |
| Contributors: |
Canadian Institutes of Health Research; Canadian Foundation for AIDS Research; International AIDS Society; National Institutes of Health |
| Source: |
Clinical Infectious Diseases ; volume 70, issue 5, page 859-866 ; ISSN 1058-4838 1537-6591 |
| Publisher Information: |
Oxford University Press (OUP) |
| Publication Year: |
2019 |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1093/cid/ciz251 |
| DOI: |
10.1093/cid/ciz251/28700752/ciz251.pdf |
| Availability: |
https://doi.org/10.1093/cid/ciz251; http://academic.oup.com/cid/advance-article-pdf/doi/10.1093/cid/ciz251/28700752/ciz251.pdf; http://academic.oup.com/cid/article-pdf/70/5/859/33432703/ciz251.pdf |
| Rights: |
https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model |
| Accession Number: |
edsbas.8B8C2D83 |
| Database: |
BASE |