biostudies-literatureSponaugle ANIAID NIH HHSNCI NIH HHSNational Institutes of Health101268https://www.ebi.ac.uk/biostudies/studies/S-EPMC10694675biostudies-literatureUnknown4(11)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 and T cell receptor (TCR) sequencing and examine proliferation to assess how ART impacts T cell homeostasis. In PWH on long-term ART, lymphocyte frequencies and phenotypes are mostly stable. By contrast, broad phenotypic changes in natural killer (NK) cells, γδ T cells, B cells, and CD4⁺ and CD8⁺ T cells are observed in the post-ART window. Whereas CD8⁺ T cells mostly restore, memory CD4⁺ T subsets and cytolytic NK cells show incomplete restoration 1.4 years post ART. Surprisingly, the 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.Cell reports. MedicineDominant CD4⁺ T cell receptors remain stable throughout antiretroviral therapy-mediated immune restoration in people with HIV.PMC10694675R37 CA247676UM1 AI069423P30 AI050410UM1 AI106701UM1 AI164567P30 CA016086UM1 AI0686345UM1AI164567UM1AI106701-08Hudgens MGArchin NMVincent BGSponaugle AAdimora AAWeideman AMKStanley NRanek JAtassi GKuritzkes DREron JJMargolis DMGay CKuruc JGoonetilleke NfalseDominant CD4⁺ T cell receptors remain stable throughout antiretroviral therapy-mediated 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 and T cell receptor (TCR) sequencing and examine proliferation to assess how ART impacts T cell homeostasis. In PWH on long-term ART, lymphocyte frequencies and phenotypes are mostly stable. By contrast, broad phenotypic changes in natural killer (NK) cells, γδ T cells, B cells, and CD4⁺ and CD8⁺ T cells are observed in the post-ART window. Whereas CD8⁺ T cells mostly restore, memory CD4⁺ T subsets and cytolytic NK cells show incomplete restoration 1.4 years post ART. Surprisingly, the 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.2023-01-01T00:00:00Z2023 Nov2026-06-17T06:40:38.462Z2025-04-19T17:02:50.769ZS-EPMC106946753794907010.1016/j.xcrm.2023.101268