Clonal replacement and differentiation of HIV-specific T-cells in people with HIV following anti-PD-1 in vivo

Antiretroviral therapy (ART) in people with HIV (PWH) is highly effective but treatment is required lifelong given the persistence of virus in a latent form as well as ongoing immune dysfunction characterized by elevated expression of the exhaustion marker Programmed cell Death protein- 1 (PD-1) on HIV-specific T cells. We isolated tetramer+ HIV-specific CD8+ T-cells from PWH on ART with cancer who received anti-PD-1 (nivolumab) every 2 weeks. and observed rapid changes following the first dose of anti-PD1, including a marked increase in the frequency of HIV-tetramer+ TEX cells in a subset of participants. Using single cell RNAseq on tetramer+ cells, we observed a distinct transcriptomic signature in tetramer+ central memory T (TCM) cells and the recruitment of multiple unique TCR clones. These findings are consistent with reinvigoration and rejuvenation of HIV-specific T-cells and evidence of clonal replacement of HIV-specific cells by anti-PD-1.