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Here, we integrated single-cell RNA and T cell receptor (TCR) sequencing data to delineate the alterations of CD8\u207a T cells. Based on cross-sectional samples from different individuals (healthy donors, treatment-na\u00efve individuals, and ART-treated individuals), we found ART promoted the transition of CD8\u207a T cells from exhausted toward na\u00efve and memory-like subsets. Weighted gene co-expression network analysis identified distinct modules, including three (SM2-SM4) highly expressed in treatment-na\u00efve individuals and one (SM6) significantly elevated post-ART. The reduced TCR diversity and increased clonality observed post-infection were not fully restored by ART, although ART partly altered clonal structure and CDR3 length. We established a predictive model based on the TCR features of CD8\u207a T cells, which accurately distinguished healthy donors, treatment-na\u00efve individuals, and ART-treated individuals. These findings clarify the complex landscape of CD8\u207a T cell reconstitution, and identify key transcriptional networks and clonal dynamics during ART.<\/jats:p>","DOI":"10.1186\/s12985-026-03212-3","type":"journal-article","created":{"date-parts":[[2026,6,7]],"date-time":"2026-06-07T05:14:15Z","timestamp":1780809255000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Single-cell characterization of the CD8+ T cell landscape and repertoire in HIV-1 Infection following antiretroviral therapy"],"prefix":"10.1186","volume":"23","author":[{"given":"Jun","family":"Lei","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Jialingfang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aifang","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,7]]},"reference":[{"key":"3212_CR1","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1146\/annurev-pathol-011110-130254","volume":"6","author":"S Moir","year":"2011","unstructured":"Moir S, Chun TW, Fauci AS. 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No patients and clinical data are involved in this study.","order":1,"name":"Ethics","label":"Ethics approval","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"191"}}