Acute hepatitis C in HIV-infected patients: rare spontaneous clearance correlates with weak memory CD4 T-cell responses to hepatitis C virus

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Abstract
Objectives: To explore the parameters of specific immunity to hepatitis C virus (HCV) associated with virus clearance during acute HCV infection in HIV coinfection. Methods: HIV-infected patients without prior HCV infection were prospectively enrolled for acute hepatitis C and followed up over 15 months. HCV-specific T cells were assessed by proliferation, ELISpot, intracellular cytokine staining and pentamer assays. Pegylated-interferon-α and ribavirin were proposed if HCV persisted at M3. Results: Thirty eight acutely HCV-infected HIV-positive patients were enrolled. HCV genotypes were predominantly 4 and 1. Five patients (13%) showed spontaneous clearance and 20 initiated treatment, of whom 13 (65%) showed sustained virologic responses. Before M3, HCV-specific proliferative responses observed in 35% cases, were associated with lower HCV viral load (P = 0.04) and predictive of spontaneous clearance (P = 0.02), particularly anti-NS4 responses (P = 0.03). These HCV-specific proliferative responses were associated with HIV-p24-specific responses (P = 0.002) independently from the HIV stage. Interferon-γ-producing T cells specific for HCV were detectable ex vivo in 81% cases but at low intensity (6 peripheral blood mononuclear cells) and were independent of the HCV outcome. Low frequencies of pentamer-positive HCV-specific CD8+ cells (0.01–0.05%) detected in nine of 12 patients were mainly effector-memory PD-1-negative T cells. Twelve days of HCV-specific in-vitro culture induced amplification of CD4 T cells coproducing interleukin-2 and interferon-γ but rarely of CD8 T cells. Conclusion: Acute HCV infection in HIV-coinfected patients is characterized by a low rate of spontaneous clearance and weak HCV-specific memory T cells, not strictly related to HIV-induced immune defects, and which correlate with virus clearance.