Article ID: JJID.2025.086
Incompletely resolved immune dysfunction in people living with HIV (PLWH) on antiretroviral treatment (ART) could differentially impact CD4+ and CD8+ T cell subsets. In this study, we investigated SARS-CoV-2 vaccine-induced CD4+ and CD8+ T cell responses in 26 PLWH on ART following third-dose mRNA vaccination. Spike-specific CD4+ and CD8+ T cell responses were assessed based on the expression of activation markers, CD137/OX40 and CD137/CD25, respectively, in response to stimulation with overlapping peptides spanning the spike protein. All participants showed spike-specific T cell responses, with CD8+ responses at a higher median frequency than CD4+. Interestingly, 5 participants who showed a higher frequency of spike-specific CD4+, relative to CD8+ T cells, were significantly younger and had higher CD4 counts pre-ART, in comparison to other participants. Further multivariate analysis revealed that only CD4 count pre-ART was an important predictor of elevated spike-specific CD4+ T cell responses; whereas no association was observed with neutralizing antibody (nAb) potency towards SARS-CoV-2 spike. Our results highlight heterogeneous immune functionality of vaccine-induced, SARS-CoV-2 spike-specific CD4+ and CD8+ T cells in PLHW on ART.
