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.
OBJECTIVE
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.
Boulassel
M R
MR
Immunodeficiency Service, Montreal Chest Institute, Royal Victoria Hospital, McGill University Health Centre, Montreal, Quebec, Canada.
Smith
G H R
GH
Edwardes
M D de B
MD
Young
M
M
Klein
M
M
Gilmore
N
N
Macleod
J
J
Leblanc
R
R
René
P
P
Allan
J
J
Lalonde
R G
RG
Routy
J P
JP
D000328:Adult; D000368:Aged; D018791:CD4 Lymphocyte Count / Q000379:methods; D018946:Chemokine CCL5 / Q000097:blood / Q000276:immunology*; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000097:blood / Q000276:immunology*; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D015851:Interleukin-7 / Q000097:blood / Q000276:immunology*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011480:Protease Inhibitors / Q000627:therapeutic use*; D016212:Transforming Growth Factor beta / Q000097:blood / Q000276:immunology*; D019562:Viral Load
C515255:CXCL12 protein, human; D018946:Chemokine CCL5; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D015851:Interleukin-7; D011480:Protease Inhibitors; D016212:Transforming Growth Factor beta