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Published on: September 6, 2019
Effective early antiretroviral therapy in perinatal-HIV infection reduces subsequent plasma inflammatory profile
Athena N Nguyen1, Alec L Plotkin1, Oludare A Odumade1,2,3
1Precision Vaccines Program, Division of Infectious Diseases, Boston Children's Hospital, Boston, MA, USA.
Insights
Starting antiretroviral therapy (ART) early in children with perinatally-acquired HIV (PHIV) dampens long-term inflammation. Early ART initiation (≤6 months) led to lower plasma inflammatory markers compared to later treatment, suggesting lasting immune benefits.
Area of Science:
- Immunology
- Virology
- Pediatrics
Background:
- Long-term immunologic effects of antiretroviral therapy (ART) in children with perinatally-acquired HIV (PHIV) require further elucidation.
- Investigating the impact of ART initiation timing on the immune profile of PHIV children is crucial.
Purpose of the Study:
- To determine how the timing of ART initiation affects the long-term immune profile of children with PHIV.
- To compare plasma cytokine, chemokine, and adenosine deaminase (ADA) levels between early and late ART treatment groups.
Main Methods:
- Compared plasma cytokine, chemokine concentrations, and ADA enzymatic activities in PHIV participants with early (≤6 months) versus late (>6 months and <2 years) ART initiation.
- Analyzed samples 12.5 years after treatment initiation.
- Correlated findings with clinical covariates.
Main Results:
- Significantly higher concentrations of 10 cytokines/chemokines (e.g., IFNγ, IL-6, CXCL10) and ADA were observed in the late-ART group compared to the early-ART group.
- ADA levels showed significant positive correlations with several pro-inflammatory cytokines (e.g., IFNγ, IL-17A, IL-12p70).
Conclusions:
- Early ART initiation (≤6 months) in PHIV children is associated with a dampened long-term plasma inflammatory profile.
- Delayed ART treatment, even with virologic suppression, is linked to persistent elevation of pro-inflammatory markers.
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.
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