Evaluation of HIV-specific T-cell responses in HIV-infected older patients with controlled viremia on long-term antiretroviral therapy

Abstract

HIV-infected older individuals may have a diminished immune response because of exhaustion/immune aging of T-cells. Therefore, 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) and achieved controlled viremia (mostly undetectable viral load; 92 patients with <20 to <40 HIV RNA copies/mL and 8 <60 to <100) and improved CD4 T-cell counts. We show that the median frequencies of HIV-specific CD4(+)and CD8(+)IFN-gamma T-cells were higher in HIV(+)than uninfected individuals (HIV-), including increasing levels of IFN-gamma produced by CD4(+)T-cells and decreasing levels by CD8(+)T-cells with increasing CD4 T-cell counts in HIV+. No correlation was found between T-cell responses and varying levels of undetectable viremia. HIV-specific TNF-alpha made by CD8(+)T-cells was higher in HIV(+)than HIV-, including decreasing levels with increasing CD4 T-cell counts in HIV+. Furthermore, the CD8(+)T-cell mediators, CD107a and Granzyme-B, were higher in HIV(+)than HIV-, and decreased with increasing CD4 T-cell counts in HIV+. Remarkably, HIV-specific CD8 T-cells produced decreasing levels of IFN-gamma with increasing age of HIV+, including decreased levels of CD107a and Granzyme-B in older HIV+. However, HIV-specific CD8(+)T-cells produced increasing levels of TNF-alpha with increasing age of the HIV+, suggesting continued inflammation. In conclusion, HIV(+)with controlled viremia on long-term ART and with higher CD4 T-cell counts showed reduced HIV-specific CD8 T-cell responses as compared to those with lower CD4 T-cell counts, and older HIV(+)exhibited decreasing levels of CD8 T-cell responses with increasing age.