CYTOKINE RESPONSE ASSOCIATED WITH HEPATITIS C VIRUS CLEARANCE IN HIV COINFECTED PATIENTS INITIATING PEG INTERFERON- BASED THERAPY.

Abstract

Background: Treatment against hepatitis C virus (HCV) infection based on peginterferon-a (pegIFNa) and ribavirin induces important changes on cytokine release and T cell activation. Objective: Immune response to pegIFNa-ribavirin therapy was explored in patients coinfected by HCV and HIV. Methods: Concentrations of 25 cytokines and CD8+ T cell activation were monitored in HCV/HIV coinfected patients classified as sustained virological responders (SVR, n=19) and non-responders (NR, n=11). Results: High pretreatment concentrations of IP-10 (CXCL-10) and MCP-1 (CCL-2) were associated with poor anti-HCV response. PegIFNa-ribavirin therapy increased CD8+ T cell activation and induced significant changes in levels of eleven cytokines related to both Th1 and Th2 responses in SVR (IL-1b, IL-1RA, IL-4, IL-5, IL-6, IL-7, IL-12p40/70, IL-13, IP-10, eotaxin, MCP-1) but only six cytokines in NR (IL-1b, IL-2, IL-5, IL-12p40/70, IL-13, eotaxin). Highest rise in MIP-1b and MCP-1 levels was observed four weeks after anti-HCV treatment initiation in SVR compared to NR (p=0.002 and p=0.03, respectively), whereas a decrease of IL-8 concentration was associated with treatment failure (p= 0.052). Conclusions: Higher and broader cytokine responses to pegIFNa-ribavirin therapy were observed in SVR patients compared to NR. Changes in IL-8, MIP-1b and MCP-1 serum concentrations may be associated with efficacy of pegIFNa- and ribavirin-based therapies in patients coinfected by HCV and HIV.

Keywords

• hepatitis C virus, HIV, cytokines