Initiating Antiretroviral Treatment Early in Infancy Has Long-term Benefits on the Human Immunodeficiency Virus Reservoir in Late Childhood and Adolescence.
HIV DNA
adolescents
children
early ART
protective HLA
Journal
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
ISSN: 1537-6591
Titre abrégé: Clin Infect Dis
Pays: United States
ID NLM: 9203213
Informations de publication
Date de publication:
06 12 2021
06 12 2021
Historique:
received:
26
10
2020
pubmed:
7
8
2021
medline:
15
3
2022
entrez:
6
8
2021
Statut:
ppublish
Résumé
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). 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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 34355738
pii: 6062433
doi: 10.1093/cid/ciaa1931
doi:
Substances chimiques
DNA, Viral
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e4214-e4222Subventions
Organisme : ANRS
Investigateurs
Mary-France Courcoux
(MF)
Catherine Dollfus
(C)
Marie-Dominique Tabone
(MD)
Geneviève Vaudre
(G)
Corinne Fourcade
(C)
Josiane Warsazawski
(J)
Jérôme Lechenadec
(J)
Olivia Dialla
(O)
Laura Nailler
(L)
Lamya Ait Si Selmi
(LAS)
Isabelle Leymarie
(I)
Thierry Wack
(T)
Alexandre Hoctin
(A)
Razika Feraon-Nanache
(R)
Isabelle Hau
(I)
Cécile Gakobwa
(C)
Véronique Avettand-Fenoël
(V)
Stéphane Blanche
(S)
Marine Fillion
(M)
Pierre Frange
(P)
Nizar Mahlaoui
(N)
Adeline Mélard
(A)
Florence Veber
(F)
Marie-Christine Mourey
(MC)
Valérie Marcou
(V)
Albert Faye
(A)
Martine Lévine
(M)
Sandrine Richard
(S)
Brigitte Autran
(B)
Assia Samri
(A)
Mariama Diallo
(M)
Sophie Caillat-Zucman
(S)
Kahina Amokrane
(K)
Rayna Ivanova-Derin
(R)
Anne Chacé
(A)
Florence Buseyne
(F)
Thomas Montange
(T)
Damien Batalie
(D)
Ingrid Fert
(I)
Asier Saez-Cirion
(A)
Valérie Monceaux
(V)
Daniel Scott-Algara
(D)
Lucie Marchand
(L)
Delphine Lebrasseur
(D)
Axel Levier
(A)
Informations de copyright
© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.