Antigen-driven clonal selection shapes the persistence of HIV-1–infected CD4+ T cells in vivo

Clonal expansion of infected CD4+ T cells is a major mechanism HIV-1 persistence and barrier to achieving cure. Potential causes are homeostatic proliferation, effects integration, interaction with antigens. Here, we show that it possible link antigen responsiveness, the full proviral sequence, integration site, cell receptor β-chain (TCRβ) sequence examine role recurrent antigenic exposure in maintaining reservoir. We isolated CMV- Gag-responding from 10 treated individuals. Proviral populations CMV-responding were dominated by large clones, including clones harboring replication-competent proviruses. TCRβ repertoires showed high clonality driven converging adaptive responses. Although some proviruses genes linked (BACH2, STAT5B, MKL1), proliferation under stimulation occurred regardless site integration. Paired analysis infection could occur early or late course clone's response generate too be explained solely proliferation. Together, these findings implicate antigen-driven clonal selection as factor persistence, finding will difficult challenge eradication efforts.