Immune control of HIV viraemia in early paediatric infection is associated with induction of HIV-specific CD8+ T-cell activity following multiple treatment interruptions

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.