Impaired Hepatitis C Virus (HCV)–Specific Interferon-γ Responses in Individuals With HIV Who Acquire HCV Infection: Correlation With CD4+ T-Cell Counts

Coinfection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) has detrimental effects on HCV disease progression, including increased HCV RNA levels, promotion of viral persistence in primary infection, and faster progression to cirrhosis and hepatocellular carcinoma [1]. HIV/HCV coinfection has also been associated with a significant reduction in the response to HCV antiviral treatment [2]. Individuals with primary HCV infection who undergo spontaneous clearance have an initial robust CD4+ helper cell response, whereas those who develop viral persistence have a poorer response, which diminishes overtime [3]. However, studies addressing the impact of coinfection on the effector function of HCV-specific T cells in acute HCV infection are limited. A small study by van den Burg et al reported a valuable role for HCV-specific CD4+ T-cell responses targeting HCV nonstructural (NS) proteins in reduction of HCV RNA (n = 2) and resolution of HCV (n = 1) in subjects with acute HIV/HCV coinfection [4]. Schnuriger et al demonstrated a similar finding, wherein HCV-specific proliferative responses (particularly against NS4) were associated with lower HCV RNA levels and spontaneous clearance of HCV in HIV/HCV-coinfected subjects [5]. Interestingly, IFN-γ responses were not associated with HCV clearance or with CD4+ T-cell counts [5]. More recently Thomson et al reported a trend for spontaneous clearance of acute HCV infection, in HIV-positive men, associated with higher CD4+ T-cell counts and stronger T-cell responses within the first 3 months of HCV infection [6]. Even fewer studies, have directly compared acute HCV-specific T-cell responses between HIV/HCV coinfection and HCV monoinfection. Danta et al demonstrated a lower frequency of HCV-specific IFN-γ production in HIV/HCV-coinfected subjects compared with internationally recruited HCV-monoinfected controls, although there was no difference in the magnitude of IFN-γ production between the cohorts [7]. These studies raise the question of whether the detrimental effects of HIV/HCV coinfection on HCV clearance could be attributed to a lack of CD4+ T-cell help, which is important in the generation and maintenance of CD8+ T-cell responses [8], to an altered cytokine environment, or both. Our objective was to determine whether the magnitude and breadth of the HCV-specific cellular immune responses in acute HCV infection is affected by HIV/HCV coinfection by directly comparing HCV-specific T-cell responses in subjects with acute HCV infection with or without HIV infection, recruited simultaneously within the Australian Trial in Acute Hepatitis C (ATAHC).