Fig. 3: Efficacy of 9 months early interventions on the sustained virologic remission in SIV-infected infant macaques when intervention is initiated at 3 days post infection.

Five newborn macaques were intravenously inoculated with identical SIVmac251 inoculum within 6 hours after birth, followed by antiretroviral therapy (ART) initiated at 3 dpi for 9 months, compared with age-matched infant macaques without treatment. a Plasma viral load in five individual SIV-infected infants on early intervention initiated at 3 dpi (colored lines, n = 5) or age-matched infant macaques without treatment (solid dark line, n = 9. Data are presented as the mean ± SEM of plasma viral load of untreated infant animals at designated timepoints). Infant NG24 was euthanized at 2 months post analytical treatment interruption (ATI) when viral rebound was observed. Four infants on early intervention showed viral remission throughout the study (up to 18 months for two infants or 3 months for another two animals off-ART to date). b Changes in peripheral CD4+ T cells gated CD3+ T-cell populations in five individual SIV-infected infants on early intervention (colored line, n = 5), compared with those of age-matched SIV-infected and untreated (solid dark line, n = 9. Data are presented as the mean ± SEM of %CD4+ T cells of untreated infant animals at specific timepoints). Peripheral CD4+ T-cell loss was observed in infant NG24 at 2 months post ATI. Levels of cell-associated total SIV RNA, total viral DNA, and integrated SIV DNA in PBMCs (c–e) and axillary LN biopsies (f–h) from five individual infant macaques on early intervention (n = 5) or untreated infant cohort post SIV infection (dark line, n = 3. Data are presented as the mean ± SEM of cell-associated SIV RNA/DNA or integrated proviral DNA in peripheral and LN tissues at designated timepoints). Colored lines represent individual neonatal animals, who were infected with SIV at birth, received early ART at 3 dpi and continued for 9 months, followed by ATI. The black line represents plasma viral load or cell-associated SIV RNA/DNA in age-matched infant animal cohorts without treatment. In situ SIV RNA + cells in axillary LN (i) and rectal (j) biopsies in five infant macaques at 2 months post ATI. SIV RNA was detected in both LN and rectal tissue of infant NG24 only. Bar, 100 μm. k Anti-SIV gp140-specific antibodies in the individual infants (n = 5) before and after ATI. Anti-SIV gp140 antibodies were detected in infant NG24 only at 2 months post ATI when viral rebound was observed. l Autologous neutralizing antibody against SIV Env in infants after 2 months of ATI (positive control/Pos Ctrl with black line included). Neutralizing antibodies were not elicited in these infants (n = 5). Data are presented as the mean ± SD of technical duplicates, representative of two independent experiments. m Absolute CD8+ T-cell numbers after anti-CD8α Ab administration and viral rebound after CD8+ cell depletion in vivo, in which plasma viral load or viral blips were not detected in the individual 4 infants up to 3 months to date. Source data are provided as a Source Data file.