Intensification with a CCR5 inhibitor at ART initiation Modulates IL-18 and Inflammation-Driven Immune Pathways in People with HIV
International Journal of Infectious Diseases, 2025
Tarazona E., Calderón-Vicente S., Fons-Contreras M., Rava M., Ruiz-Sancho A., Rivero A., Macías J., Olalla J., Vidal B., Díaz D., Alcamí J., Muriel A., Serrano-Villar S., Moreno S.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Infectious Diseases | Pathophysiology | Plasma |  Olink Target 96 |
Abstract
Purpose
Persistent inflammation in people with HIV (PWH) on antiretroviral therapy (ART) may drive comorbidities and disease progression. Since CCR5 signalling regulates viral entry and immune activation, maraviroc (MVC) may contribute to attenuate inflammation, though previous findings have been inconsistent. This study evaluated a broad panel of markers to assess the long-term immunomodulatory effects of MVC when added at ART initiation.
Methods
We conducted a longitudinal observational study including PWH starting ART with MVC (MVC group, n=14) or without MVC (Non-MVC group, n=28), matched by sex, age and ART regimen. Plasma markers were quantified by Proximity Extension Assay (PEA) and ELISA methods. Mixed multivariate models analyzed marker dynamics, and functional analyses identified enriched biological pathways.
Results
PEA showed significant variation in up to fifteen inflammatory markers (e.g., CXCL9, CXCL10, IFN-γ, CCL19) among both groups over ART initiation. Moreover, IL-18 declined significantly only in the MVC group (17.6% per year by PEA, and 35.5% by ELISA, p-value<0.05). Functional Enrichment analyses showed a stronger downregulation of inflammation-related pathways, particularly the chemokine signalling, in the MVC group (q-value<0.05).ConclusionOur results suggest that MVC intensification at ART initiation might contribute to reducing IL-18 levels and inflammation-driven immune pathways, providing insights for strategies to mitigate persistent inflammation in PWH.