Towards an HBV cure: state-of-the-art and unresolved questions-report of the ANRS workshop on HBV cure.

Affiliations ECOFECTInternational audienceHBV infection is a major cause of liver cirrhosis and hepatocellular carcinoma. Although HBV infection can be efficiently prevented by vaccination, and treatments are available, to date there is no reliable cure for the >240 million individuals that are chronically infected worldwide. Current treatments can only achieve viral suppression, and lifelong therapy is needed in the majority of infected persons. In the framework of the French National Agency for Research on AIDS and Viral Hepatitis 'HBV Cure' programme, a scientific workshop was held in Paris in June 2014 to define the state-of-the-art and unanswered questions regarding HBV pathobiology, and to develop a concerted strategy towards an HBV cure. This review summarises our current understanding of HBV host-interactions leading to viral persistence, as well as the roadblocks to be overcome to ultimately address unmet medical needs in the treatment of chronic HBV infection

A randomized, placebo-controlled, blind anti-AIDS clinical trial: Safety and immunogenicity of a specific anti-IFNα immunization

HIV-induced cytokine dysregulation, incluCling overproduction of the antiproliferative and cytolytic IFNα cytokine, represents a major component of the immune disorders characterizing AIDS. To block the overproduction of IFNα we designed an AIDS vaccine combination which included both an anti-HIV and/or an anti-IFNα immunization. The safety and immunogenicity of this multicomponent vaccine were tested in mice, Cercopithecus, two HIV noninfected individuals, and six HIV-1 seropositive immunocompromised patients enrolled in a 1-year open clinical trial. We now report the result of a 9-month short-term randomized, blind, placebo-controlled clinical trial (Phase I/II) performed in HIV-1 patients (22 individuals) to confirm safety/tolerance of the anti-IFNα vaccine and its immunogenicity and to evaluate whether the complex vaccine initially used could be simplified by removal of HIV compo-nent(s). Three groups of patients received inactivated IFNα (i-IFNα) associated with the immunomodulator P40 with HIV-1 antigens (groups B and C) or without (group A), and one group (D) was placebo. The clinical follow-up documented among those receiving i-IFNα showed that none developed AIDS and/or required antiretroviral chemotherapy. Viral load did not increase and CD4 cell count as well as cell-mediated immunity (CMI) stabilized or even significantly increased in group A. Immunogenicity of the preparations was determined by a positive delayed-type hypersensitivity (DTH) reaction to i-IFNα and the presence of serum antibodies to i-IFNα and to HIV-1 peptides, occurring only in treated patients. As previously planned, based on these safety data, the trial has been extended for an additional year and all patients were switched to protocol A (i-IFNα + P40). This second period of the trial, now open and ongoing, should allow us to evaluate further the innocuity of the i-IFNα preparation and whether anti-IFNα vaccine could provide a long-lasting CD4 cell count as well as CMI stabilization. © 1994 Raven Press Ltd. New York.SCOPUS: ar.jinfo:eu-repo/semantics/publishe