Reduction in terminally differentiated T cells in virologically controlled HIV-infected aging patients on long-term antiretroviral therapy

Several studies have shown an increased accumulation of terminally differentiated T cells during HIV infection, suggestive of exhaustion/senescence, causing dysregulation of T cell homeostasis and function and rapid HIV disease progression. We have investigated whether long-term antiretroviral therapy (ART), which controls viremia and restores CD4 T cell counts, is correlated with reduction in terminally differentiated T cells, improved ratios of naïve to memory and function of T cells in 100 virologically controlled HIV-infected patients. We show that while the median frequencies of terminally differentiated CD4(+) and CD8(+) T cells (CD28(-), CD27(-), CD57(+) and CD28(-)CD57(+)), were higher in the virologically controlled HIV-infected patients’ cohort compared with uninfected individuals’ cohort, the frequencies of these cells significantly decreased with increasing CD4 T cell counts in HIV-infected patients. Although, the naïve CD4(+) and CD8(+) T cells were lower in HIV patients’ cohort than uninfected cohort, there was a significant increase in both naïve CD4(+) and CD8(+) T cells with increasing CD4 T cell counts in HIV-infected patients. The underlying mechanism behind this increased naïve CD4(+) and CD8(+) T cells in HIV-infected patients was due to an increase in recent thymic emigrants, CD4(+)CD31(+), as compared to CD4(+)CD31(-). The CD4(+) T cells of HIV-infected patients produced cytokines, including IL-2, IL-10 and IFN-γ comparable to uninfected individuals. In conclusion, virologically controlled HIV-infected patients on long-term ART show a significant reduction in terminally differentiated T cells, suggestive of decreased exhaustion/senescence, and improvement in the ratios of naïve to memory and function of T cells.