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Multicenter Study
. 2020 Feb 14;70(5):859-866.
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

Ari Bitnun  1 , Doris G Ransy  2 , Jason Brophy  3 , Fatima Kakkar  4 , Michael Hawkes  5 , Lindy Samson  3 , Bayader Annabi  2   6 , Amélie Pagliuzza  7 , Jacob-Adams Morand  2   6 , Laura Sauve  8 , Nicolas Chomont  6   7 , Stephanie Lavoie  9 , John Kim  9 , Paul Sandstrom  9 , Paul A Wender  10 , Terry Lee  11 , Joel Singer  11   12 , Stanley E Read  1 , Hugo Soudeyns  2   6 ; Early Pediatric Initiation Canada Child Cure Cohort (EPIC4) Research Group
Collaborators, Affiliations
Multicenter Study

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 et al. Clin Infect Dis. .

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.

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Figures

Figure 1.
Figure 1.
Impact of age of initiation of effective cART on the size of the viral reservoir, measured by quantitative assay of HIV-1 DNA in PBMCs (A), copies of HIV-1 RNA produced by prostratin analogue stimulated CD4+ T-cells (B), and quantitative HIV-1–specific serologic response in children with perinatally acquired HIV-1 infection (C). The horizontal lines correspond to the median and IQR. The significant and nonsignificant differences between groups were retained in the analysis adjusted for biological sex, CD4% nadir, VL peak, and virologic blips (data not shown). Abbreviations: cART, combination antiretroviral therapy; HIV-1, human immunodeficiency virus–1; IQR, interquartile range; PBMCs, peripheral blood mononuclear cells; VL, viral load.
Figure 2.
Figure 2.
Correlation of HIV-1 reservoir size in PBMC measured using the HIV-1 DNA assay and cell-free HIV-1 RNA in CD4+ T-cells using the prostratin analogue stimulation assay. Abbreviations: HIV-1, human immunodeficiency virus–1; PBMC, peripheral blood mononuclear cell.
See this image and copyright information in PMC

References

    1. Strain MC, Little SJ, Daar ES, et al. . Effect of treatment, during primary infection, on establishment and clearance of cellular reservoirs of HIV-1. J Infect Dis 2005; 191:1410–8. - PubMed
    1. Jain V, Hartogensis W, Bacchetti P, et al. . Antiretroviral therapy initiated within 6 months of HIV infection is associated with lower T-cell activation and smaller HIV reservoir size. J Infect Dis 2013; 208:1202–11. - PMC - PubMed
    1. Laanani M, Ghosn J, Essat A, et al. ; Agence Nationale de Recherche sur le Sida PRIMO Cohort Study Group Impact of the timing of initiation of antiretroviral therapy during primary HIV-1 infection on the decay of cell-associated HIV-DNA. Clin Infect Dis 2015; 60:1715–21. - PubMed
    1. Persaud D, Patel K, Karalius B, et al. ; Pediatric Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome Cohort Study Influence of age at virologic control on peripheral blood human immunodeficiency virus reservoir size and serostatus in perinatally infected adolescents. JAMA Pediatr 2014; 168:1138–46. - PMC - PubMed
    1. Foster C, Pace M, Kaye S, et al. ; CHERUB Investigators Early antiretroviral therapy reduces HIV DNA following perinatal HIV infection. AIDS 2017; 31:1847–51. - PubMed

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