Viral suppression is associated with rising NT-proCNP levels and reduced systemic inflammation in people living with HIV

BACKGROUND: People living with HIV (PLWH) have an increased risk of cardiovascular disease that persists despite effective antiretroviral therapy (ART) and viral suppression. Chronic inflammation and endothelial dysfunction are central contributors, yet integrative biomarkers linking viral activity, inflammation, and vascular homeostasis remain poorly defined. N-terminal pro-C-type natriuretic peptide (NT-proCNP), a marker of endothelial function and cardiovascular stress, is responsive to inflammatory states, and is processed by furin, a protease also required for viral entry. Data on NT-proCNP in PLWH are scarce. The aim of this study was to investigate longitudinal changes in NT-proCNP in relation to HIV viral load and systemic inflammation in PLWH starting ART. METHODS: In this exploratory longitudinal observational study, we included PLWH aged ≥ 18 years with initial diagnosis of HIV between 09/2023 and 06/2025. Before and approximately 3 months after initiation of ART plasma NT-proCNP, furin, and a multiplex panel of inflammatory cytokines were measured alongside HIV viral load, CD4⁺ T-cell count, serum creatinine, and C-reactive protein. Paired comparisons were performed using the Wilcoxon matched-pairs signed-rank test with false discovery rate (FDR) correction using the Benjamini-Krieger-Yekutieli method (Q = 5%). Correlations between longitudinal changes were explored using Spearman analysis with FDR adjustment. RESULTS: NT-proCNP concentrations increased significantly over time (33.7 [25.3-40.7] vs. 39.4 [31.2-55], p = 0.006), while a broad range of inflammatory cytokines showed significant reduction after FDR correction. Circulating furin concentrations did not change significantly. Correlation analyses between changes in NT-proCNP and individual inflammatory or virological markers were not significant after FDR correction. CONCLUSION: In this study we present first-time data on the impact of the initiation of ART on the levels and dynamics of NT-proCNP in PLWH. Suppression of HIV replication is accompanied by reduced systemic inflammation and a significant increase in circulating NT-proCNP, suggesting the restoration of vascular homeostatic signaling during early follow-up. NT-proCNP may represent an integrative biomarker linking viral control, inflammation, and cardiovascular biology in HIV infection, warranting further investigation in larger prospective studies with clinical cardiovascular endpoints. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION: NCT02149004, 23.05.2014.