{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T10:34:23Z","timestamp":1788258863028,"version":"build-2803163510"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,3,28]],"date-time":"2023-03-28T00:00:00Z","timestamp":1679961600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Perinatally acquired HIV infection (PHIV) occurs during a critical window of immune development. We investigated changes in systemic inflammation and immune activation in adolescents with PHIV and those without HIV (HIV-) in Uganda.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A prospective observational cohort study was performed in 2017-2021 in Uganda. All participants were between 10-18 years of age and without active co-infections. PHIVs were on ART with HIV-1 RNA level \u2264400 copies\/mL. We measured plasma and cellular markers of monocyte activation, T-cell activation (expression of CD38 and HLA-DR on CD4+ and CD8+), oxidized LDL, markers of gut integrity and fungal translocation. Groups were compared using Wilcoxon rank sum tests. Changes from baseline were examined with 97.5% confidence intervals on relative fold change. P values were adjusted for false discovery rate.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We enrolled 101 PHIV and 96 HIV-; among these, 89 PHIV and 79 HIV- also had measurements at 96 weeks. At baseline, median (Q1, Q3) age was 13 yrs (11,15), and 52% were females. In PHIV, median CD4+ cell counts were 988 cells\/\u00b5L (638, 1308), ART duration was 10 yrs (8, 11), and 85% had viral load &amp;lt;50 copies\/mL throughout the study, 53% of participants had a regimen switch between visits, 85% of whom switched to 3TC, TDF and DTG. Over 96 weeks, while hsCRP decreased by 40% in PHIV (p=0.12), I-FABP and BDG both increased by 19 and 38% respectively (p=0.08 and \u22640.01) and did not change in HIV- (p\u22650.33). At baseline, PHIVs had higher monocyte activation (sCD14) (p=0.01) and elevated frequencies of non-classical monocytes (p&amp;lt;0.01) compared to HIV- which remained stable over time in PHIV but increased by 34% and 80% respectively in HIV-. At both time points, PHIVs had higher T cell activation (p \u2264 0.03: CD4+\/CD8+ T cells expressing HLA-DR and CD38). Only in PHIV, at both timepoints, oxidized LDL was inversely associated with activated T cells(p&amp;lt;0.01). Switching to dolutegravir at week 96 was significantly associated an elevated level of sCD163 (\u03b2=0.4, 95% CI=0.14,0.57, p&amp;lt;0.01), without changes in other markers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Ugandan PHIV with viral suppression have some improvement in markers of inflammation over time, however T-cell activation remains elevated. Gut integrity and translocation worsened only in PHIV over time. A deeper understanding of the mechanisms causing immune activation in ART treated African PHIV is crucial.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1165964","type":"journal-article","created":{"date-parts":[[2023,3,28]],"date-time":"2023-03-28T04:38:25Z","timestamp":1679978305000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":17,"title":["Persistent immune activation and altered gut integrity over time in a longitudinal study of Ugandan youth with perinatally acquired 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