Elevated IP10 levels are associated with immune activation and low CD4+ T-cell counts in HIV controller patients

Abstract

Although HIV controllers (HICs) achieve long-term control of viremia in the absence of antiretroviral therapy (ART), they display marked immune activation. The levels of inflammatory biomarkers in HICs and the biomarkers' relationships with immunologic and virologic status have yet to be fully characterized. A cohort study. Plasma levels of seven biomarkers [tumor necrosis factor (TNF)α, interleukin (IL)6, IL10, interferon gamma-induced protein 10 (IP10), monocyte chemoattractant protein-1 (MCP1), soluble CD14 (sCD14), soluble CD163 (sCD163)] were compared in 70 HICs, 33 HIV-1-infected, treatment-naive noncontrollers (viremic patients), 30 ART-treated patients and 40 healthy donors. In HICs, we investigated the interplay between biomarkers, cell activation and the CD4⁺ T-cell count. HICs had higher levels of IP10, TNFα and sCD14 than healthy donors did (P < 0.01 for each). Also, TNFα and sCD14 levels of the HICs were similar to those measured in viremic and ART-treated patients. However, the levels of IL6 and IL10 were significantly lower in HICs than in viremic or ART-treated patients. In HICs, only IP10 levels differed significantly from those in both healthy donors and viremic patients, and were positively correlated with the expression of CD8⁺ and CD4⁺ T-cell activation markers. The IP10 levels of HICs were still elevated 12 and 24 months after the initial assay. Lastly, IP10 levels at enrollment were negatively correlated with the CD4⁺ T-cell count at enrollment and 12 months later. HICs display a number of inflammatory features associated with persistent T-cell immune activation.