Immune control of HIV viraemia in early paediatric infection is associated with induction of HIV-specific CD8+ T-cell activity following multiple treatment interruptions
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ID: 327276
2026
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Abstract
BACKGROUND: Virus-specific CD8+ T-cells play an important part in HIV cure/remission in adults, yet their role in paediatric immune control is limited by tolerogenic early-life immunity. Very-early ART initiation, while effective in restricting viral reservoir size, also prevents antigenic exposure and, thereby, the induction of HIV-specific CD8+ T-cell responses. Analytical treatment interruption (ATI) is an established tool in cure/remission studies for assessing time to viral rebound and viral setpoint off ART yet the impact of ATI on HIV-specific immune responses and plasma viral load (pVL) remains understudied in paediatric populations. METHODS: We evaluated a historical randomised cohort of early ART-treated children in South Africa. Infants with HIV were randomized to either Arm-1, receiving an initial course of ART followed by three short, pVL-guided treatment interruptions, or Arm-2, receiving continuous ART. Both arms then underwent an extended ATI in the second year of life. Virological outcomes, viral sequencing, and HIV-specific T-cell responses were assessed longitudinally. RESULTS: During the extended ATI, Arm-1 participants, following multiple treatment interruptions, demonstrated a lower peak and set-point pVL compared to Arm-2, alongside an early induction of HIV-specific CD8+ T-cell responses. One Arm-1 participant achieved undetectable pVL for 1.5 months during the extended ATI, before losing immune control associated with viral escape within dominant Gag CD8+ T-cell epitopes. CONCLUSIONS: Short-term viral exposure from serial ATIs is associated with the induction and/or boosting of HIV-specific CD8+ T-cell responses and enhanced immune control of HIV in early ART-treated children.
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openalex_W7204627881
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| Authors | Julia Edgar, Harriet R Parker, Christina Thobakgale, Emily Adland, Andrew J. Prendergast, Gareth Tudor-Williams, Henrik N. Kløverpris, Søren Buus, Bruce D Walker, Thumbi Ndung’u, Krista Dong, Photini Kiepiela, Philip Goulder |
| Journal | The Journal of infectious diseases |
| Year | 2026 |
| DOI |
10.1093/infdis/jiag440
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| URL | |
| Keywords | Keywords not found |
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