TY - JOUR
T1 - Cytokine trajectory over time in men and women with HIV on long-term ART
AU - Vanpouille, Christophe
AU - Wells, Alan
AU - Degruttola, Victor
AU - Lynch, Miranda
AU - Zhang, Xinlian
AU - Fitzgerald, Wendy
AU - Tu, Xin
AU - Chaillon, Antoine
AU - Landay, Alan
AU - Weber, Kathleen
AU - Scully, Eileen
AU - Karn, Jonathan
AU - Gianella, Sara
N1 - Publisher Copyright:
© 2024 Wolters Kluwer Health, Inc.
PY - 2024
Y1 - 2024
N2 - 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 40cytokines/chemokines in 31 men and 59 women who maintained viral suppression over a median period of 6years (317 visits ranging 24 to 384weeks 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 9 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.Conclusions:Our study reveals a continuous decline in markers of monocyte/macrophage activation over six 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.
AB - 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 40cytokines/chemokines in 31 men and 59 women who maintained viral suppression over a median period of 6years (317 visits ranging 24 to 384weeks 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 9 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.Conclusions:Our study reveals a continuous decline in markers of monocyte/macrophage activation over six 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.
KW - ART
KW - cytokine
KW - HIV
KW - macrophage
KW - monocyte
KW - plasma
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U2 - 10.1097/QAD.0000000000004033
DO - 10.1097/QAD.0000000000004033
M3 - Article
C2 - 39639719
AN - SCOPUS:85208229849
SN - 0269-9370
JO - AIDS
JF - AIDS
M1 - 10.1097/QAD.0000000000004033
ER -