Journal Article

HIV-specific CD8+ T-cell proliferative response 24 weeks after early antiretroviral therapy initiation is associated with the subsequent reduction in the viral reservoir

van Crevel, Reinout, Vogt, Liffert, Kootstra, Neeltje A, Nijhuis, Monique, Boeser-Nunnink, Brigitte, Klouwens, Michelle J, Lungu, Cynthia, Mahmoudi, Tokameh, Prins, Jan M, van Paassen, Pien Margien, Rokx, Casper, Symons, Jori, de Bree, Godelieve J, Maurer, Irma, Bolluyt, Dita C, Buchholtz, Ninée VEJ, Pasternak, Alexander O, van Dort, Karel A, van der Veen, Annelou LIP, van Nuenen, Ad C

2026

Overview

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.