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Anti-hepatitis C virus (HCV) treatment combining IFN-alpha and ribavirin (IFN+R) has still poorly defined effects on immune responses. Frequencies of T helper (Th) type 1 cells specific for HCV, cytomegalovirus (CMV) and HIV were measured in chronically HCV-infected patients with or without HIV co-infection during IFN+R treatment. Although scarce, peripheral blood HCV-specific Th1 cells did not change significantly, while frequencies of HIV and CMV-specific Th1 cells decreased in co-infected patients independently of CD4 cell count changes. This suggests that IFN+R therapy might compromise virus-specific immune defenses in immunosuppressed patients.

Objectives: To compare the T-cell responses to hepatitis C virus (HCV) and HIV in HIV-infected long-term non-progressors (LT-NP) and HIV-positive progressors co-infected with HCV and in HIV-negative HCV-infected patients., Methods: Three groups were studied: 10 HCV/HIV-infected LT-NP, 26 HCV/HIV-infected progressors and 13 HCV-infected/HIV-negative patients. Virus-specific CD4 and CD8 T-cell responses in peripheral blood were assessed by interferon (IFN)-gamma Elispot assays using recombinant proteins (HIV-p24 and three HCV antigens) and 16 HIV or HCV HLA A3- and/or HLA A2-restricted cytotoxic T lymphocytes peptides. Statistical analysis was performed with non-parametric tests., Results: In addition to high T helper 1 (Th1) cell frequencies directed against HIV-p24, LT-NP had significantly (P < 0.05) higher frequencies of Th1 cells against HCV than the two other groups. No difference was observed between HIV-infected progressors and HIV-negative controls. Furthermore, HCV-specific CD4 and CD8 T cells were correlated in LT-NP (P = 0.006)., Conclusion: Thus, independently of the HIV-related immune alterations, LT-NP of the HIV-infection might have an intrinsic capacity to develop strong Th1 cell responses to viruses, particularly HIV and HCV.

Objective: Although discrepancies between histological and virological responses to anti-hepatitis C virus (HCV) therapy are well-established in HIV-negative patients, the liver histological outcome has never been assessed in HIV-HCV co-infected patients receiving anti-HCV therapy. We compared histological responses to interferon (IFN) alpha therapy between HIV-positive and HIV-negative injecting drug users (IDU) and determined factors associated with histological response., Design: Retrospective cohort study., Setting: Hepatology unit of a tertiary referral hospital., Patients/interventions: Seventy-nine HCV-infected IDU (32 HIV-positive) receiving a 6-month course of IFN-alpha2b therapy, 3 x 106 U three times a week., Primary Outcome Measure: Histological response, defined by a > or =2 point decrease in total Knodell score measured on paired liver biopsies over a 2-year follow-up period., Results: The sustained response rate to IFN therapy was lower in HIV-positive patients than in HIV-negative patients (6.2% versus 29.8%;P = 0.012). Conversely, the rates of histological response (40.6% versus 36.2%) were not different between HIV-positive and HIV-negative patients. Independent factors associated with histological response were first total Knodell score (P = 0.0007) and sustained response to IFN therapy (odds ratio, 12.34; P = 0.005). Histological response was observed in 25% of IFN non-responders whatever their HIV status. In HIV-positive patients, the CD4 cell count did not influence the histological response., Conclusions: in HIV-HCV co-infected patients treated with IFN, liver histological improvement is frequently observed, similarly to that observed in HIV-negative patients. Such beneficial effect of interferon therapy supports early treatment of chronic hepatitis C in HIV-infected patients.