Christophe Vanpouille, Alan Wells, Victor DeGruttola, Miranda Lynch, Xinlian Zhang, Wendy Fitzgerald, Xin Tu, Antoine Chaillon, Alan Landay, Kathleen M Weber, Eileen Scully, Jonathan Karn, Sara Gianella
{"title":"Cytokine trajectory over time in men and women with HIV on long-term antiretroviral therapy.","authors":"Christophe Vanpouille, Alan Wells, Victor DeGruttola, Miranda Lynch, Xinlian Zhang, Wendy Fitzgerald, Xin Tu, Antoine Chaillon, Alan Landay, Kathleen M Weber, Eileen Scully, Jonathan Karn, Sara Gianella","doi":"10.1097/QAD.0000000000004033","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>Although antiretroviral therapy (ART) suppresses viral replication and reduces inflammation, it does not lead to the normalization of cytokines. The long-term effects of ART beyond viral suppression have not been studied and are mostly limited to cross-sectional research.</p><p><strong>Design: </strong>The impact of long-term ART on the trajectory of 40 cytokines/chemokines in 31 men and 59 women who maintained viral suppression over a median period of 6 years (317 visits ranging from 24 to 384 weeks post ART initiation) were measured by Luminex.</p><p><strong>Methods: </strong>We used a generalized additive model with a Gaussian distribution and identity link function to model concentrations over time and investigate sex and race differences.</p><p><strong>Results: </strong>While most cytokine/chemokine trajectories remained stable, the trajectory of nine markers of monocyte/macrophage activation (IP-10, I-TAC, MIG, sCD163, sCD14, MCP-1, MIP-3β, CXCL13, TNF-α) decreased over time (adj. P < 0.05). Despite continuous viral suppression, M-CSF, IL-15, and LBP increased over time (adj. P < 0.05). sCD14 was the only cytokine whose trajectory differed by sex (adj. P = 0.033). Overall, women had lower mean levels of IL-18 but higher levels of sCD14 than did men (adj. P < 0.05). GROα, LBP, and sCD14 showed significant differences between races (adj. P < 0.05). No association between cytokines and cellular HIV DNA/RNA was found.</p><p><strong>Conclusion: </strong>Our study reveals a continuous decline in markers of monocyte/macrophage activation over 6 years of suppressive ART, indicating that long-term treatment may mitigate inflammaging and cardiovascular-related outcomes. The higher levels of sCD14 observed in women are consistent with them having greater innate immune activation than men do.</p>","PeriodicalId":7502,"journal":{"name":"AIDS","volume":"39 1","pages":"1-10"},"PeriodicalIF":3.4000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11631044/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"AIDS","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/QAD.0000000000004033","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/10/10 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Objective: Although antiretroviral therapy (ART) suppresses viral replication and reduces inflammation, it does not lead to the normalization of cytokines. The long-term effects of ART beyond viral suppression have not been studied and are mostly limited to cross-sectional research.
Design: The impact of long-term ART on the trajectory of 40 cytokines/chemokines in 31 men and 59 women who maintained viral suppression over a median period of 6 years (317 visits ranging from 24 to 384 weeks post ART initiation) were measured by Luminex.
Methods: We used a generalized additive model with a Gaussian distribution and identity link function to model concentrations over time and investigate sex and race differences.
Results: While most cytokine/chemokine trajectories remained stable, the trajectory of nine markers of monocyte/macrophage activation (IP-10, I-TAC, MIG, sCD163, sCD14, MCP-1, MIP-3β, CXCL13, TNF-α) decreased over time (adj. P < 0.05). Despite continuous viral suppression, M-CSF, IL-15, and LBP increased over time (adj. P < 0.05). sCD14 was the only cytokine whose trajectory differed by sex (adj. P = 0.033). Overall, women had lower mean levels of IL-18 but higher levels of sCD14 than did men (adj. P < 0.05). GROα, LBP, and sCD14 showed significant differences between races (adj. P < 0.05). No association between cytokines and cellular HIV DNA/RNA was found.
Conclusion: Our study reveals a continuous decline in markers of monocyte/macrophage activation over 6 years of suppressive ART, indicating that long-term treatment may mitigate inflammaging and cardiovascular-related outcomes. The higher levels of sCD14 observed in women are consistent with them having greater innate immune activation than men do.
期刊介绍:
Publishing the very latest ground breaking research on HIV and AIDS. Read by all the top clinicians and researchers, AIDS has the highest impact of all AIDS-related journals. With 18 issues per year, AIDS guarantees the authoritative presentation of significant advances. The Editors, themselves noted international experts who know the demands of your work, are committed to making AIDS the most distinguished and innovative journal in the field. Submitted articles undergo a preliminary review by the editor. Some articles may be returned to authors without further consideration. Those being considered for publication will undergo further assessment and peer-review by the editors and those invited to do so from a reviewer pool.