Longitudinal transcriptomic analysis of SIV-infected rhesus macaques reveals peripheral immune dynamics throughout untreated SIV infection and long-term antiretroviral therapy

Further, we uncover transcriptional signatures suggestive of unresolved immune dysregulation during long-term suppressive therapy – most prominently among myeloid cell populations. By examining concurrent measurements of intact proviral DNA, we link peripheral responses to reservoir size via IPDA. We furthermore identify ribosomal-associated pathways as key differentiators of infection stage, treatment status, and time on ART.

Finally, we tested whether previously published transcriptional correlates of differential outcomes (e.g. viral rebound, vaccine efficacy) changed over time on ART. Overall, our findings capture dynamic immune remodeling from acute infection through long-term ART, highlighting complexities in achieving complete immune recovery that may influence future therapeutic strategies.