Influence of RANTES, SDF-1 and TGF-β levels on the value of interleukin-7 as a predictor of virological response in HIV-1-infected patients receiving double boosted protease inhibitor-based therapy

Objectives: Interleukin-7 (IL-7), RANTES (regulated on activation, normal T cell expressed and secreted), stromal cell-derived factor-1 (SDF-1) and transforming growth factor-beta (TGF-β) appear to share certain biological properties in vitro and all are involved in HIV-1 disease progression. Our earlier observations indicated that IL-7 levels decrease upon CD4 T-cell recovery and represent a new, independent predictor of virological response. Here, we examine associations among circulating levels of IL-7, RANTES, SDF-1 and TGF-β in hopes of gaining insight into their contribution to the predictive value of IL-7. Methods: Levels of IL-7, RANTES, SDF-1 and TGF-β, and immune and viral parameters were assessed in HIV-1-infected patients. Results: Cross-sectional (n = 148) and longitudinal (n = 36) analyses showed that levels of IL-7, but not RANTES, SDF-1 or TGF-β, were increased in HIV-1-infected adults compared with those of healthy controls. In the cross-sectional study, levels of IL-7 were correlated with RANTES (r = 0.31, P = 0.002) and TGF-β (r= 0.53, P<0.001) but not with SDF-1 (r=0.12, P=0.22), and these associations were more pronounced in patients with CD4 T-cell counts > 200 cells/μL. In contrast to IL-7, levels of RANTES, SDF-1 and TGF-β were not correlated with CD4 T-cell counts. Longitudinal analysis revealed a marked decline in IL-7 levels accompanied by an increase in CD4 T-cell count following antiretroviral therapy (ART), but no changes in RANTES, SDF-1 or TGF-β levels. Multivariate regression analysis showed no influence of baseline RANTES, SDF-1 or TGF-β levels on the value of IL-7 as a predictor of virological response at 48 weeks. Conclusions: Collectively, these results indicate that changes in IL-7 levels did not induce changes in RANTES, SDF-1 or TGF-β. Furthermore, they indicate that RANTES, SDF-1 or TGF-β levels do not explain the predictor value of IL-7 in patients receiving ART.