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Studies examining the effect of HIV/HCV co-infection on the HCV-specific immune response in acute HCV infection are limited. This study directly compared acute HCV-specific T cell responses and cytokine profiles between 20 HIV/HCV co-infected and 20 HCV mono-infected subjects, enrolled in the Australian Trial in Acute Hepatitis C (ATAHC), using HCV peptide ELISpot and multiplex in vitro cytokine production assays. HIV/HCV co-infection had a detrimental effect upon the HCV-specific cytokine production in acute HCV infection, particularly on HCV-specific IFN-gammaproduction (magnitude p=0.004, breadth p=0.046), which correlated with peripheral CD4 counts (rho=0.605, p=0.005), but not with detectable HIV viraemia (rho=0.152, p=0.534).