Dominant CD4+ T cell receptors remain stable throughout antiretroviral therapymediated immune restoration in people with HIV

In people with HIV (PWH), the post antiretroviral therapy (ART) window is critical for immune restoration and HIV reservoir stabilization. We employ deep immune profiling, T cell receptor (TCR) sequencing and examine proliferation to assess how ART impacts T cell homeostasis. Hierarchies and frequencies of dominant CD4 TCR clonotypes (0.1-11% of all CD4+ T cells) remain stable post-ART, suggesting that clonal homeostasis can be independent of homeostatic processes regulating CD4+T cell absolute number, phenotypes and function. The slow restoration of host-immunity post-ART also has implications for the design of ART interruption studies. Cohort A5248 were people with HIV who had just initiated antiretroviral therapy and were followed for 504 days. In this group (n=4 participants) we examined TCRβ clonotype diversity in CD4 T cells at 5 timepoints between Day 0 and 504. Cohort LT-ART were people with HIV who had been durably suppressed on antiretroviral therapy for an average of 6.7 years. In this group (n=3 participants) we examined TCRβ clonotype diversity in CD4 T cells at 3 timepoints over a 1.5 year window.