Effective early antiretroviral therapy in perinatal-HIV infection reduces subsequent plasma inflammatory profile

BackgroundThe 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.

Automated summary

This study investigates the long-term immune profile of children with perinatally-acquired HIV (PHIV) by measuring plasma cytokines, chemokines, and adenosine deaminases (ADAs) and how it is affected by the timing of antiretroviral therapy (ART) initiation. The results show significant differences in plasma cytokine, chemokine, and ADA concentrations between early-ART and late-ART treatment groups. Early treatment appears to dampen the long-term inflammatory profile in PHIV participants.