HIV-specific CD8+ T-cell responses soon after treatment initiation during acute HIV infection are associated with viral reservoir decline

van Paassen, P. M.; Pasternak, A. O.; van Dort, K. A.; van Nuenen, A. C.; Maurer, I.; Boeser-Nunnink, B.; Buchholtz, N. V. E. J.; Mahmoud, T.; Lungu, C.; van Crevel, R.; Rokx, C.; Symons, J.; Nijhuis, M.; van der Veen, A. L. I. P.; Vogt, L.; Klouwens, M. J.; Prins, J. M.; Kootstra, N. A.; de Bree, G. J.

doi:10.1101/2025.02.24.639839

bioRxiv · 10.1101/2025.02.24.639839

HIV-specific CD8+ T-cell responses soon after treatment initiation during acute HIV infection are associated with viral reservoir decline

van Paassen, P. M.·Pasternak, A. O.·van Dort, K. A.·van Nuenen, A. C.·Maurer, I.·Boeser-Nunnink, B.·Buchholtz, N. V. E. J.·Mahmoud, T.·Lungu, C.·van Crevel, R.·Rokx, C.·Symons, J.·Nijhuis, M.·van der Veen, A. L. I. P.·Vogt, L.·Klouwens, M. J.·Prins, J. M.·Kootstra, N. A.·de Bree, G. J.

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Abstract

Antiretroviral therapy (ART) initiated in the acute phase of HIV infection (AHI) results in a smaller viral reservoir. However, the impact of early HIV-specific T-cell responses on long- term reservoir dynamics is less well characterized. Therefore, we measured the size of the viral reservoir and functionality of HIV-specific CD8+ T-cell responses after the acute phase at 24 and 156 weeks after ART initiation in individuals who started treatment during AHI. A significant reduction in total and defective HIV DNA and a trend towards a reduction in intact HIV DNA were observed between 24 and 156 weeks. Functional CD8+ T-cell responses against HIV peptides Env, Gag, Nef, and Pol were maintained over three years after treatment initiation. The proliferative capacity of HIV-specific CD8+ T cells at 24 weeks of ART was predictive of the degree of reduction in total and defective HIV DNA between 24 and 156 weeks, suggesting HIV-specific CD8+ T-cells may at least partially drive the decline of the viral reservoir. Therefore, enforcing HIV-specific immune responses as early as possible after diagnosis of AHI should be a central focus of HIV cure strategies.

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van Paassen, P. M., Pasternak, A. O., van Dort, K. A., van Nuenen, A. C., Maurer, I., Boeser-Nunnink, B., Buchholtz, N. V. E. J., Mahmoud, T., Lungu, C., van Crevel, R., Rokx, C., Symons, J., Nijhuis, M., van der Veen, A. L. I. P., Vogt, L., Klouwens, M. J., Prins, J. M., Kootstra, N. A., de Bree, G. J.. 2025-03-01. HIV-specific CD8+ T-cell responses soon after treatment initiation during acute HIV infection are associated with viral reservoir decline. https://doi.org/10.1101/2025.02.24.639839

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