HIV-specific CD8+ T-cell proliferative response 24 weeks after early antiretroviral therapy initiation is associated with the subsequent reduction in the viral reservoir
2026
Pien Margien van Paassen | Alexander O Pasternak | Dita C Bolluyt | Karel A van Dort | Ad C van Nuenen | Irma Maurer | Brigitte Boeser-Nunnink | Ninée VEJ Buchholtz | Tokameh Mahmoudi | Cynthia Lungu | Reinout van Crevel | Casper Rokx | Jori Symons | Monique Nijhuis | Annelou LIP van der Veen | Liffert Vogt | Michelle J Klouwens | Jan M Prins | Neeltje A Kootstra | Godelieve J de Bree
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 people with HIV who started treatment during AHI. A significant reduction in total and defective HIV DNA and a trend toward 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 3 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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