Cytokine Response Associated with Hepatitis C Virus Clearance in HIV Coinfected Patients Initiating Peg Interferon-α Based Therapy

BACKGROUND: Treatment of hepatitis C virus (HCV) infection based on peginterferon-α (pegIFNα) and ribavirin induces important changes in cytokine release and T cell activation. OBJECTIVE: Immune response to pegIFNα-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 a poor anti-HCV response. PegIFNα-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-1β, IL-1RA, IL-4, IL-5, IL-6, IL-7, IL-12p40/70, IL-13, IP-10, eotaxin, MCP-1) but of only six cytokines in NR (IL-1β, IL-2, IL-5, IL-12p40/70, IL-13, eotaxin). The highest rise in MIP-1β 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 in IL-8 concentration was associated with treatment failure (p= 0.052). CONCLUSIONS: Higher and broader cytokine responses to pegIFNα-ribavirin therapy were observed in SVR patients compared to NR. Changes in IL-8, MIP-1β, and MCP-1 serum concentrations may be associated with efficacy of pegIFNα- and ribavirin-based therapies in patients coinfected by HCV and HIV.