TY - JOUR
T1 - Initiating Antiretroviral Treatment Early in Infancy Has Long-term Benefits on the Human Immunodeficiency Virus Reservoir in Late Childhood and Adolescence
AU - the ANRS-EP59-CLEAC Study Group
AU - Avettand-Fenoel, Véronique
AU - Lechenadec, Jérôme
AU - Diallo, Mariama Sadjo
AU - Fillion, Marine
AU - Melard, Adeline
AU - Samri, Assia
AU - Dollfus, Catherine
AU - Blanche, Stéphane
AU - Faye, Albert
AU - Amokrane, Kahina
AU - Autran, Brigitte
AU - Buseyne, Florence
AU - Warszawski, Josiane
AU - Frange, Pierre
AU - Courcoux, Mary France
AU - Dollfus, Catherine
AU - Tabone, Marie Dominique
AU - Vaudre, Geneviève
AU - Fourcade, Corinne
AU - Warsazawski, Josiane
AU - Lechenadec, Jérôme
AU - Dialla, Olivia
AU - Nailler, Laura
AU - Selmi, Lamya Ait Si
AU - Leymarie, Isabelle
AU - Wack, Thierry
AU - Hoctin, Alexandre
AU - Feraon-Nanache, Razika
AU - Hau, Isabelle
AU - Gakobwa, Cécile
AU - Avettand-Fenoël, Véronique
AU - Fillion, Marine
AU - Frange, Pierre
AU - Mahlaoui, Nizar
AU - Mélard, Adeline
AU - Veber, Florence
AU - Mourey, Marie Christine
AU - Marcou, Valérie
AU - Faye, Albert
AU - Lévine, Martine
AU - Richard, Sandrine
AU - Autran, Brigitte
AU - Samri, Assia
AU - Diallo, Mariama
AU - Caillat-Zucman, Sophie
AU - Amokrane, Kahina
AU - Ivanova-Derin, Rayna
AU - Chacé, Anne
AU - Buseyne, Florence
AU - Montange, Thomas
N1 - Publisher Copyright:
© The Author(s) 2021.
PY - 2021/12/1
Y1 - 2021/12/1
N2 - Background. Early combined antiretroviral therapy (cART) limits the total HIV-DNA load in children. However, data on its impact in older children and adolescents remain scarce. This study compares HIV reservoirs in children (5–12 years) and adolescents (13–17 years) who started cART <6 months (early [E-] group) or >2 years (late [L-] group). Methods. The ANRS-EP59-CLEAC study prospectively enrolled 76 patients perinatally infected with HIV-1 who reached HIV-RNA <400 copies/mL <24 months after cART initiation, regardless of subsequent viral suppression (E-group: 27 children, 9 adolescents; L-group: 19 children, 21 adolescents). Total and integrated HIV-DNA were quantified in blood and in CD4+ T-cell subsets. A substudy assessed HIV reservoir inducibility after ex vivo peripheral blood mononuclear cell (PBMC) stimulation. Results. Total HIV-DNA levels were lower in early-versus late-treated patients (children: 2.14 vs 2.87 log copies/million PBMCs; adolescents: 2.25 vs 2.74 log; P < .0001 for both). Low reservoir was independently associated with treatment precocity, protective HLA, and low cumulative viremia since cART initiation. The 60 participants with undetectable integrated HIV-DNA started cART earlier than other patients (4 vs 54 months; P = .03). In those with sustained virological control, transitional and effector memory CD4+ T cells were less infected in the E-group than in the L-group (P = .03 and .02, respectively). Viral inducibility of reservoir cells after normalization to HIV-DNA levels was similar between groups. Conclusions. Early cART results in a smaller blood HIV reservoir until adolescence, but all tested participants had an inducible reservoir. This deserves cautious consideration for HIV remission strategies.
AB - Background. Early combined antiretroviral therapy (cART) limits the total HIV-DNA load in children. However, data on its impact in older children and adolescents remain scarce. This study compares HIV reservoirs in children (5–12 years) and adolescents (13–17 years) who started cART <6 months (early [E-] group) or >2 years (late [L-] group). Methods. The ANRS-EP59-CLEAC study prospectively enrolled 76 patients perinatally infected with HIV-1 who reached HIV-RNA <400 copies/mL <24 months after cART initiation, regardless of subsequent viral suppression (E-group: 27 children, 9 adolescents; L-group: 19 children, 21 adolescents). Total and integrated HIV-DNA were quantified in blood and in CD4+ T-cell subsets. A substudy assessed HIV reservoir inducibility after ex vivo peripheral blood mononuclear cell (PBMC) stimulation. Results. Total HIV-DNA levels were lower in early-versus late-treated patients (children: 2.14 vs 2.87 log copies/million PBMCs; adolescents: 2.25 vs 2.74 log; P < .0001 for both). Low reservoir was independently associated with treatment precocity, protective HLA, and low cumulative viremia since cART initiation. The 60 participants with undetectable integrated HIV-DNA started cART earlier than other patients (4 vs 54 months; P = .03). In those with sustained virological control, transitional and effector memory CD4+ T cells were less infected in the E-group than in the L-group (P = .03 and .02, respectively). Viral inducibility of reservoir cells after normalization to HIV-DNA levels was similar between groups. Conclusions. Early cART results in a smaller blood HIV reservoir until adolescence, but all tested participants had an inducible reservoir. This deserves cautious consideration for HIV remission strategies.
KW - Adolescents
KW - Children
KW - Early ART
KW - HIV DNA
KW - Protective HLA
UR - http://www.scopus.com/inward/record.url?scp=85105363157&partnerID=8YFLogxK
U2 - 10.1093/cid/ciaa1931
DO - 10.1093/cid/ciaa1931
M3 - Article
C2 - 34355738
AN - SCOPUS:85105363157
SN - 1058-4838
VL - 73
SP - E4214-E4222
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 11
ER -