GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE278nnn/GSE278091/primaryOK200TranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE278091GEOGSEfalseClonal replacement and differentiation of HIV-specific T-cells in people with HIV following anti-PD-1 in vivoAntiretroviral 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-1.2026/06/04GSE278091GSM8539510GSM8539511GSM8539501GSM8539512GSM8539513GSM8539502GSM8539503GSM8539514GSM8539515GSM8539504GSM8539516GSM8539505GSM8539506GSM8539517GSM8539518GSM8539507GSM8539508GSM853950930209278091Homo sapiens