{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T00:52:33Z","timestamp":1781139153332,"version":"3.54.1"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T00:00:00Z","timestamp":1747008000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010877","name":"Science, Technology and Innovation Commission of Shenzhen Municipality","doi-asserted-by":"publisher","award":["JCYJ20220531102202005"],"award-info":[{"award-number":["JCYJ20220531102202005"]}],"id":[{"id":"10.13039\/501100010877","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2024A1515012118"],"award-info":[{"award-number":["2024A1515012118"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>High-density lipoprotein cholesterol (HDL-C) is a well-established marker of lipid metabolism and increasingly recognized as an indicator of inflammatory status. This study investigates HDL-C\u2019s role as a predictor of immune reconstitution in people living with HIV (PLWH).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed a prospective cohort study of 15,434 PLWH initiating antiretroviral therapy at the Third People\u2019s Hospital of Shenzhen, China, between 2005 and 2022. Baseline quartile grouping and Group-Based Trajectory Modeling (GBTM) explored the relationship between HDL-C and immune reconstitution. Restricted cubic spline plots identified nonlinear association.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Over a median follow-up of 17.9 months, 9,609 PLWH achieved the CD4+ T-cell count of 500 cells\/\u03bcL or higher. Multivariate-adjusted Cox proportional hazards regression model showed that hazard ratios (HR) [95% confidence intervals (CI)] for CD4+ T-cell recovery in Q2, Q3, and Q4 versus Q1 of the HDL-C were 0.94 (95% CI: 0.88-0.99), 0.92 (95% CI: 0.87-0.98), and 0.85 (95% CI: 0.80-0.91), respectively. GBTM identified two HDL-C trajectories: Low-floating and High-floating. Relative to Low-floating, High-floating demonstrated a reduced likelihood of CD4+ T-cell recovery (HR=0.86, 95% CI: 0.82-0.90, p &amp;lt; 0.001). A nonlinear association was observed between HDL-C and the outcome (p for nonlinear association = 0.037, p for overall &amp;lt; 0.001), with a threshold at 1.13 mmol\/L. Negative correlations between HDL-C and CD4+ T-cell recovery were observed both below the threshold (HR=0.72, 95% CI: 0.57-0.92) and above the threshold (HR=0.78, 95% CI: 0.69-0.87) (both p &amp;lt; 0.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our study highlights HDL-C\u2019s role in immune recovery, suggesting its potential in guiding prevention and treatment strategies for PLWH.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1520615","type":"journal-article","created":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T05:40:06Z","timestamp":1747028406000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["HDL-C as a novel predictor of immune reconstitution in people living with HIV: insights from a baseline-to-dynamic change cohort study in China, 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