Fig. 3

Chromatin modification and safe harbor regions are preferential sites for HIV integration in the Acute-ART group than AIDS-ART group but are more prone to loss during treatment. a Distribution of HIV integration across genomic regions. The bar chart compares the frequency of HIV proviral DNA integration into in-gene regions versus upstream promoter regions (TSS up) in PLWH initiating ART during the acute stage (n = 54, red) and those in the AIDS stage (n = 36, blue). No significant differences are observed in the distribution of integration sites in host genome between the two groups (left). The accompanying table indicates that ART in the acute-phase group, 47.8% (3299) of integrations occur in in-gene regions, and 26.5% (1833) in upstream promoter regions. In contrast, in the AIDS group, 50.0% (2692) of integrations occur in in-gene regions, with 25.8% (1394) in upstream promoter regions (right). b Chromosomal distribution of HIV integration sites. The bar chart illustrates the distribution of HIV integration across different chromosomes in both groups, revealing no obvious variation between those initiating ART during the acute phase (red) and the AIDS stage (blue). c–f Cumulative preference for HIV integrated UIS into chromatin regions over time. The comparison shows the percentage of HIV integration in all patients from two groups: those initiating ART during the acute phase (red) and those in the AIDS stage (blue) (left panels). The cumulative curves illustrate the preference for HIV integration into different genomic regions over time (y-axis representing cumulative % in UIS, x-axis representing months) (right panels). These regions include chromatin modifications (c), in-gene regions (d), enhancer regions (e), and safe harbor regions (f). g, h Mosaic chart of UIS distribution across chromatin modification and in-gene regions among different disease groups. This mosaic chart displays the UIS in Chromatin modification region (g) and in-genes region (h) in four groups—Acute-initiated ART (≤12 months and >12 months) and AIDS-stage initiated ART (≤12 months and >12 months) (left panel). The bar charts in (g) and (h) display the total UIS clonal sizes across various time periods (right panel). i Normalized and Log-transformed clonal percentage of UIS into region of in-gene regions (left panel) and chromatin modification (right panel) in four groups. j Donut charts illustrating HIV integration preferences across different groups. PLWH who initiate ART within the first 12months of the acute stage show a higher number of UIS integrated into chromatin modification regions (blue), and more UIS integrated into safe harbor regions (yellow) and CpG islands (orange) beyond 12 months in Acute-ART group. In contrast, PLWH initiating ART after 12 months during the AIDS stage exhibit fewer of these clonal UIS types, with integration primarily occurring in in-gene regions (red). (Note: Distinct dots represented as each measurement in each bar chart and data are represented as mean ± SEM; p < 0.05 indicates statistical significance; Wilcoxon test for (c–f) left panel; random linear regression test for (c–f) right panel; 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)