Nguyen, Athena N.Plotkin, Alec L.Odumade, Oludare A.Armas, Lesley dePahwa, SavitaMorrocchi, ElenaCotugno, NicolaRossi, PaoloTagarro García, AlfredoEPIICAL ConsortiumEt al.2024-02-042024-02-042023Nguyen, A. N., Plotkin, A. L., Odumade, O. A., De Armas, L., Pahwa, S., Morrocchi, E., Cotugno, N., Rossi, P., Foster, C., Domínguez-Rodríguez, S., Tagarro, A., Syphurs, C., Diray-Arce, J., Fatou, B., Ozonoff, A., Levy, O., Palma, P., Smolen, K. K., on the behalf of the EPIICAL Consortium (2023). Effective early antiretroviral therapy in perinatal-HIV infection reduces subsequent plasma inflammatory profile. Pediatric Research, 94(5), 1667-1674. https://doi.org/10.1038/s41390-023-02669-00031-39981530-0447http://hdl.handle.net/11268/12652BackgroundThe 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).Methods40 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.ResultsPlasma concentrations of 10 cytokines and chemokines (IFN gamma, 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 IFN gamma, IL-17A, and IL-12p70. Meanwhile, total ADA was positively correlated with IFN gamma, IL-13, IL-17A, IL-1RA, IL-6, and IL-12p70 as well as CCL7.ConclusionsElevation 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.ImpactThis 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., IFN gamma, 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.engAntirretroviralesPlasmajournal article10.1038/s41390-023-02669-0restricted accessSidaPediatría