Delayed loss of control of plasma lipopolysaccharide levels after therapy interruption in chronically HIV-1-infected patients

Objective: Increased circulating levels of lipopolysaccharide (LPS) have been demonstrated in HIV-1-infected progressors. We investigated the effect of antiretroviral therapy (ART) interruptions on plasma LPS levels. Design and methods: Overall, 77 individuals participated in this Study (51 HIV-positive and 26 healthy). Ten out of 51 HIV-positive participants were viremic ART-naive patients and 41 Out of 51 were chronically Suppressed patients on ART (three or more drugs, CD4 cell Count more than 400 cells/mu l, HIV-1 RNA less than 500 copies/ml for more than 8 months, less than 50 copies/ml at recruitment) undergoing therapy interruption. The limulus amebocyte assay was used to measure plasma LPS levels; enzyme-linked immunosorbent assay to measure plasma levels of endotoxin-core antibodies (FndoCAb), soluble (s)CD14, LPS-binding protein and IFN-alpha; immunoblotting to measure plasma gelsolin levels; and same day whole blood flow cytometry to measure levels of T-cell-activation markers (CD8(+)/CD38(+), CD8(+)/HLA-DR+ andCD3(+)/CD95(+)). Results: Increases in viremia and T-cell-activation markers were observed during therapy interruptions. During short-term therapy interruptions of less than 12 weeks, no change in LPS levels was found, whereas negative associations between viral load and LPS levels (Spearman's Rho=-0.612, P=0.0152), viral load and EndoCAb change (triangle EndoCAb, correlation=-0.502, P=0.0204), and between triangle LPS and triangle EndoCAb (correlation=-0.851, P=0.0073) were observed. In contrast, increased LPS (P=-0.0171) and sCD14 (P<0.0001) levels were observed during long-term therapy interruption of more than 12 weeks compared with levels during ART, together with no association between I PS and viral load or EndoCAb. No association between immune activation and LPS was evident at any time point. Conclusion: Increased plasma LPS levels were observed only after more than 12 weeks of ART interruption, despite presence of LPS-controlling host mechanisms. (c) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins