Evaluation of HIV-Specific T-Cell Responses in HIV-Infected Aging Patients with Controlled Viremia on Long-term Antiretroviral Therapy

Abstract

Abstract While long-term antiretroviral therapy (ART) has helped many human immunodeficiency virus type 1 (HIV-1) infected aging patients to achieve controlled viremia and restored CD4 T-cell counts, the role of HIV-specific T-cell responses in these patients is not clearly understood. We have investigated HIV-specific CD4 and CD8 T-cell responses in 100 HIV-infected patients (HIV+) who have aged on long-term antiretroviral therapy (ART) with controlled viremia and restored CD4 T-cell counts. We show the median circulating HIV-specific CD4+ and CD8+IFN-γ T-cells in HIV+ were higher than uninfected controls (HIV−), including increased levels of HIV-specific CD4+IFN-γ T-cells and decreased levels of CD8+IFN-γ T-cells with increasing CD4T-cell counts in HIV+. In addition, HIV-specific CD8+TNF-α T-cells were higher in HIV+ than HIV−, including decreasing levels were seen with increasing CD4T-cell counts of HIV+. Furthermore, the CD8+ T-cell mediators, Granzyme B and CD107a, were higher in HIV+ than HIV−, however these mediators decreased with increasing CD4 T-cell counts in HIV+. More importantly, HIV-specific CD4+ and CD8+ T-cells produced higher levels of IFN-γ and CD8+ T-cells TNF-α, Granzyme B and CD107a with increasing age of HIV+ probably to counter residual HIV and reduced immunity in older individuals. In conclusion, while HIV-infected patients with controlled viremia and improved CD4 T-cell counts showed reduced CD8 T-cell responses, the CD8 T-cell responses were higher in HIV+ with lower CD4 T-cell counts as well as in HIV+ patients with increasing age.