Influence of RANTES, SDF-1 and TGF-beta 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

HIV Med. 2005 Jul;6(4):268-77. doi: 10.1111/j.1468-1293.2005.00306.x.

Abstract

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-beta) 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-beta 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-beta, 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-beta, 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-beta (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/microL. In contrast to IL-7, levels of RANTES, SDF-1 and TGF-beta 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-beta levels. Multivariate regression analysis showed no influence of baseline RANTES, SDF-1 or TGF-beta 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-beta. Furthermore, they indicate that RANTES, SDF-1 or TGF-beta levels do not explain the predictor value of IL-7 in patients receiving ART.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • CD4 Lymphocyte Count / methods
  • Chemokine CCL5 / blood
  • Chemokine CCL5 / immunology*
  • Chemokine CXCL12
  • Chemokines, CXC / blood
  • Chemokines, CXC / immunology*
  • Cross-Sectional Studies
  • Disease Progression
  • Female
  • HIV Infections / drug therapy
  • HIV Infections / immunology*
  • HIV Infections / virology
  • HIV-1 / immunology*
  • Humans
  • Interleukin-7 / blood
  • Interleukin-7 / immunology*
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Prospective Studies
  • Protease Inhibitors / therapeutic use*
  • Transforming Growth Factor beta / blood
  • Transforming Growth Factor beta / immunology*
  • Viral Load

Substances

  • CXCL12 protein, human
  • Chemokine CCL5
  • Chemokine CXCL12
  • Chemokines, CXC
  • Interleukin-7
  • Protease Inhibitors
  • Transforming Growth Factor beta