Effective early antiretroviral therapy in perinatal-HIV infection reduces subsequent plasma inflammatory profile.
Journal
Pediatric research
ISSN: 1530-0447
Titre abrégé: Pediatr Res
Pays: United States
ID NLM: 0100714
Informations de publication
Date de publication:
11 2023
11 2023
Historique:
received:
17
11
2022
accepted:
02
05
2023
revised:
14
04
2023
medline:
6
11
2023
pubmed:
13
6
2023
entrez:
12
6
2023
Statut:
ppublish
Résumé
The long-term immunologic effects of antiretroviral therapy (ART) in children with perinatally-acquired HIV (PHIV) have not been fully elucidated. Here, we investigated how the timing of ART initiation affects the long-term immune profile of children living with PHIV by measuring immunomodulatory plasma cytokines, chemokines, and adenosine deaminases (ADAs). 40 PHIV participants initiated ART during infancy. 39 participant samples were available; 30 initiated ART ≤6 months (early-ART treatment); 9 initiated ART >6 months and <2 years (late-ART treatment). We compared plasma cytokine and chemokine concentrations and ADA enzymatic activities between early-ART and late-ART treatment 12.5 years later and measured correlation with clinical covariates. Plasma concentrations of 10 cytokines and chemokines (IFNγ, IL-12p70, IL-13, IL-17A, IL-IRA, IL-5, IL-6, and IL-9 as well as CCL7, CXCL10), ADA1, and ADA total were significantly higher in late-ART compared to early-ART treatment. Furthermore, ADA1 was significantly positively correlated with IFNγ, IL-17A, and IL-12p70. Meanwhile, total ADA was positively correlated with IFNγ, IL-13, IL-17A, IL-1RA, IL-6, and IL-12p70 as well as CCL7. Elevation of several pro-inflammatory plasma analytes in late-ART despite 12.5 years of virologic suppression compared to early-ART treatment suggests that early treatment dampens the long-term plasma inflammatory profile in PHIV participants. This study examines differences in the plasma cytokine, chemokine, and ADA profiles 12.5 years after treatment between early (≤6months) and late (>6 months and <2 years) antiretroviral therapy (ART) treatment initiation in a cohort of European and UK study participants living with PHIV. Several cytokines and chemokines (e.g., IFNγ, IL-12p70, IL-6, and CXCL10) as well as ADA-1 are elevated in late-ART treatment in comparison to early-ART treatment. Our results suggest that effective ART treatment initiated within 6 months of life in PHIV participants dampens a long-term inflammatory plasma profile as compared to late-ART treatment.
Sections du résumé
BACKGROUND
The long-term immunologic effects of antiretroviral therapy (ART) in children with perinatally-acquired HIV (PHIV) have not been fully elucidated. Here, we investigated how the timing of ART initiation affects the long-term immune profile of children living with PHIV by measuring immunomodulatory plasma cytokines, chemokines, and adenosine deaminases (ADAs).
METHODS
40 PHIV participants initiated ART during infancy. 39 participant samples were available; 30 initiated ART ≤6 months (early-ART treatment); 9 initiated ART >6 months and <2 years (late-ART treatment). We compared plasma cytokine and chemokine concentrations and ADA enzymatic activities between early-ART and late-ART treatment 12.5 years later and measured correlation with clinical covariates.
RESULTS
Plasma concentrations of 10 cytokines and chemokines (IFNγ, IL-12p70, IL-13, IL-17A, IL-IRA, IL-5, IL-6, and IL-9 as well as CCL7, CXCL10), ADA1, and ADA total were significantly higher in late-ART compared to early-ART treatment. Furthermore, ADA1 was significantly positively correlated with IFNγ, IL-17A, and IL-12p70. Meanwhile, total ADA was positively correlated with IFNγ, IL-13, IL-17A, IL-1RA, IL-6, and IL-12p70 as well as CCL7.
CONCLUSIONS
Elevation of several pro-inflammatory plasma analytes in late-ART despite 12.5 years of virologic suppression compared to early-ART treatment suggests that early treatment dampens the long-term plasma inflammatory profile in PHIV participants.
IMPACT
This study examines differences in the plasma cytokine, chemokine, and ADA profiles 12.5 years after treatment between early (≤6months) and late (>6 months and <2 years) antiretroviral therapy (ART) treatment initiation in a cohort of European and UK study participants living with PHIV. Several cytokines and chemokines (e.g., IFNγ, IL-12p70, IL-6, and CXCL10) as well as ADA-1 are elevated in late-ART treatment in comparison to early-ART treatment. Our results suggest that effective ART treatment initiated within 6 months of life in PHIV participants dampens a long-term inflammatory plasma profile as compared to late-ART treatment.
Identifiants
pubmed: 37308683
doi: 10.1038/s41390-023-02669-0
pii: 10.1038/s41390-023-02669-0
doi:
Substances chimiques
Interleukin-17
0
Interleukin-13
0
Interleukin-6
0
Anti-Retroviral Agents
0
Cytokines
0
Chemokines
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1667-1674Investigateurs
Carlo Giaquinto
(C)
Silvia Faggion
(S)
Daniel Gomez Pena
(DG)
Inger Lindfors Rossi
(IL)
William James
(W)
Alessandra Nardone
(A)
Federica D'Ambrosio
(F)
Paola Zangari
(P)
Carla Paganin
(C)
Eleni Nastouli
(E)
Moira Spyer
(M)
Anne-Genevieve Marcelin
(AG)
Vincent Calvez
(V)
Pablo Rojo
(P)
Maria Angeles Munoz
(MA)
Anita De Rossi
(A)
Mark Cotton
(M)
Nigel Klein
(N)
Deborah Persaud
(D)
Rob J De Boer
(RJ)
Juliane Schroeter
(J)
Adriana Ceci
(A)
Viviana Giannuzzi
(V)
Kathrine Luzuriaga
(K)
Louise Kuhn
(L)
Andrew Yates
(A)
Avy Violari
(A)
Kennedy Otwombe
(K)
Paula Vaz
(P)
Maria Grazia Lain
(MG)
Elisa López-Varela
(E)
Tacilta Nhamposssa
(T)
Elisa Lopez
(E)
Denise Naniche
(D)
Philip Goulder
(P)
Mathias Lichterfeld
(M)
Holly Peay
(H)
Pr Mariam Sylla
(PM)
Almoustapha Maiga
(A)
Thanyawee Puthanakit
(T)
Cissy Kityo
(C)
Informations de copyright
© 2023. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.
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