Fig. 5

HIV provirus integrated into TSGs is more likely to result in monoclonal expansion in AIDS-ART group, posing a higher cancer risk compared to those in Acute-ART group. a PCA plot analysis of monoclonal UIS. The PCA plot highlights differences in monoclonal UIS between Acute-ART group (dots) and AIDS-ART group (crosses). All the monoclonal UIS clustered into 3 group, A, B and C. Blue indicates PLWH with ART duration over 12 months, while red indicates those with ART duration of less than 12 months. b, c Ranked GSEA of clusters A and C based on clonal normalized size, with similarity analysis on the top 100 enriched pathways, distilled to 15 key pathways and their associated core genes (upper panel). The x-axis represents clonal normalized size, while the y-axis shows the top 100 enriched pathways. The heatmap (lower panel) illustrates the 15 key pathways and corresponding core genes within each pathway for the Acute-ART group (b) and the AIDS-ART group (c). d Cumulative curve of individuals percentage with TSGs monoclonal during ART duration. The cumulative curves displayed the percentage of individuals with TSGs monoclonal (y-axis) over time (x-axis) in the Acute-ART group (red line) versus AIDS-ART group (blue line), illustrate the preference for HIV integration into TSGs over time. e Mosaic chart of TSG monoclonal UIS distribution. This chart illustrates the relative percentage of TSGs monoclonal in two groups—Acute-ART group (left, n = 54) and AIDS-ART group (right, n = 36). A larger block area indicates a higher prevalence and greater homogeneity of TSGs monoclonal, while a smaller block area reflects increased heterogeneity in clonal distribution patterns. f The bar chart shows the comparison of the percentage of TSGs monoclonal among all PLWH from two groups: those initiating ART during the acute phase (red) and those during the AIDS stage (blue). g, h TSGs integrated by HIV to be monoclonal UIS. List of UIS (count percent < 40%) into TSGs, when disrupted by HIV integration into in-genes region and subjected to clonal expansion, become monoclonal types. This poses a greater cancer risk in Acute-ART group (g) compared to AIDS-ART group (h). (Note: p < 0.05 indicates statistical significance; Wilcoxon test for (f); Random linear regression for (d); the terms ‘Acute’ and ‘AIDS’ in all figures refer to PLWH who initiated ART during the acute stage (also referred to as the Acute-ART group) and those who initiated ART during the AIDS stage (also referred to as the AIDS-ART group), respectively)