Research Paper Volume 18 pp 5—29

HIV+ART accelerates intrinsic aging in naïve CD8 T cells while maintaining stable cell type proportions. (A) Predicted cell types using the cell type prediction model (n = 6 controls; n = 8 donors with HIV). (B) Heatmap of canonical marker expression across predicted subsets validates the cell type predictions. Markers include CD8A, CD4, CCR7, GZMB, GNLY, and FOXP3. (C) Predicted age of individual T cells versus chronological age of donors shows a low correlation (R = 0.14, MAE = 13.6 years, p < 1 × 10⁻¹⁶). (D) Averaged predicted donor ages versus chronological age shows a strong correlation (R = 0.66, MAE = 12.6 years, p =.002). (E–J) Proportional changes in each T cell subset due to HIV + ART. (K–P) Residual age prediction by condition for each cell type due to HIV + ART. (Q, R) Gene-level analysis of shared transcriptional signatures between HIV + ART and aging in naïve and effector CD8 T cells. Correlations are shown with regression lines (orange) and statistical significance marked in blue. Statistical significance is indicated: ^*** Bonferroni-corrected p-value less than or equal to .001, ^* Bonferroni-corrected P-value less than or equal to .05, ^# Bonferroni-corrected P-value less than or equal to .1.