Figure 1: CHER trial median time of ART received by treatment arm from participants of this study. Light green marks early ART start, orange indicates median time o ART (either before initiation in the deferred arm, or during interruption in the early treatment arms), and dark green represents ART restart aer planned treatment interruption or ART start of continuous ART in the deferred arm. e data reects that of the substudy only, not the CHER trial overall. Median ART interruption time was 13 weeks (IQR = 9.3-248) for Early 40W, and 92 weeks [IQR = 14.3-152] for Early 96W arms. Median deferred time of ART start was 26.1 weeks for Deferred arm [22,23].

Figure 2: Median telomere length, thymic and naïve B-cell output of South African children from the CW Clinic, from birth to 10 years of age. Dynamic change of telomere length (A; n = 152), thymic (B; n = 149) and naïve B-cell output (C; n = 117). Weighted best-t lines generated using R, with a 95% condence interval. Telomere length based on the z-score for weight (D). Error bars represent the 95% condence intervals. Kruskal-Wallis test, Bonferroni-adjusted p-value marked with an asterisk indicate statistical signicance (<0.05*; <0.01**)

Figure 3: Telomere length per chromosome end (kb) in South African children without HIV (CWC) and children with HIV (CHER). A) Comparison between groups based on age (2 or 5 years old). Difference in TL between CWC and CHER based on ART regime, at 2 (B) and 5 (C) years old. D) Progression of TL from 2 to 5 years of age in CHER participants under different arm treatments. Correlation between the age-adjusted TL with the percentage of lifetime on ART in CHER study participants on the ART-deferred (orange), Early-40W (light blue) and Early-96W (dark blue) groups, at 2 (E) and 5 (F) years old. Error bars represent the 95% confidence intervals. Kruskal-Wallis test, Bonferroni-adjusted p-value marked with an asterisk indicate statistical significance (<0.05*; <0.01**; <0.001***; <0.0001****).

Figure 4: Telomere length per chromosome end (kb) in South African children at 2 years of age based on the helper (CD4) and cytotoxic (CD8) T-cell immune activation (HLADR) and proliferation (Ki67) levels. Comparison between children without HIV (CWC) with normal or high immune activation/proliferation and children with perinatally acquired HIV (CHER). TL based on the immune activation levels in CD4+ (A) and CD8+ (B) T-cells; and based on the immune proliferation levels in CD4+ (C) and CD8+ (D) T-cells. Error bars represent the 95% confidence intervals. Kruskal-Wallis test, Bonferroni-adjusted p-- value marked with an asterisk indicate statistical significance (<0.05*; <0.01**; <0.001***; <0.0001****).

Figure 5: Percentage of immune activated (HLADR) and proliferating (Ki67) T-cells in South African children at 2 years. Comparison between children without HIV (CWC) with normal or high immune activation/proliferation and children with perinatally acquired HIV (CHER). Percentage of immune activated helper (CD4+ ; A) and cytotoxic (CD8+ ; B) T-cells. Percentage of immune proliferating helper (C) and cytotoxic (D) T-cells. Error bars represent the 95% condence intervals. Kruskal-Wallis test, Bonferroni-adjusted p-value marked with an asterisk indicate statistical signicance (<0.05*; <0.01**; <0.001***; <0.0001****).