Plasma Levels of Secreted Cytokines in Virologically Controlled HIV-Infected Aging Adult Individuals on Long-Term Antiretroviral Therapy.

Abstract

HIV-infected (HIV⁺) aging adult individuals who have achieved undetectable viral load and improved CD4 T cell counts due to long-term antiretroviral therapy (ART) may continue to experience inflammation and immunosenescence. Therefore, we evaluated the plasma levels of proinflammatory and anti-inflammatory cytokines in 173 HIV⁺ aging adult individuals with age ranging from 22 to 81 years on long-term ART with viral load mostly <20 HIV RNA copies/mL and compared with 92 HIV-uninfected (HIV^- or healthy controls) aging individuals. We found that the median levels of TNF-α, IFN-γ, IL-1β, IL-6, and IL-10 were higher (p < 0.001 to <0.0001) and IL-17 trended lower in HIV⁺ individuals than healthy controls. Increasing CD4 T cell counts in the HIV⁺ cohort did not significantly change the circulating cytokine levels, although levels of IL-1β increased. However, IL-17 levels significantly decreased with increasing CD4 counts in the healthy controls and yet unchanged in the HIV⁺ cohort. Of note, the levels of circulating IL-17 were significantly reduced comparatively in the healthy controls where the CD4 count was below 500, yet once above 500 the levels of CD4, IL-17 levels were comparable with the HIV⁺ cohort. With increasing CD8 T cell counts, the levels of these cytokines were not significantly altered, although levels of TNF-α, IFN-γ, and IL-6 declined, whereas IL-1β and IL-17 were slightly elevated. Furthermore, increasing age of the HIV⁺ cohort did not significantly impact the cytokine levels although a slight increase in TNF-α, IL-6, IL-10, and IL-17 was observed. Similarly, these cytokines were not significantly modulated with increasing levels of undetectable viral loads, whereas some of the HIV⁺ individuals had higher levels of TNF-α, IFN-γ, and IL-1β. In summary, our findings show that HIV⁺ aging adult individuals with undetectable viral load and restored CD4 T cell counts due to long-term ART still produce higher levels of both proinflammatory and anti-inflammatory cytokines compared with healthy controls, suggesting some level of inflammation.